HIFU Ablation of Soft Tissue Sarcoma

NCT05111964 | Recruiting

• 1 other identifier: 15182
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Around 3,300 people are diagnosed with soft tissue sarcoma (STS) each year in the UK, and a significant proportion of STS diagnoses are in people aged under 30 years. STS can arise from various tissue types and is comprised of over 50 tumour types. Although STS is treated with a combination of surgery, radiotherapy and chemotherapy, the prognosis is relatively poor with a five-year survival rate of 54%. There is an unmet need for further treatment modalities in STS. High intensity focused ultrasound (HIFU) is a non-invasive way of treating cancers with minimal side effects, low complication rate and quick recovery. Ultrasound waves are used to destroy tumour cells and improvements in technology and experience are enabling complete destruction of tumour. HIFU also releases tumour antigens, increasing the immune response against cancer. HIFU has received FDA approvals for several indications, including bone metastases and we are using a CE-approved HIFU device in Oxford (UKCA-approvals anticipated for 2023). There have been some publications from China showing promise in STS, however this technology needs further evaluation within the UK's healthcare setting. This study will recruit patients with both resectable and unresectable STS, in addition to unresectable small symptomatic desmoid tumours. 12-16 patients, and a minimum of 10 patients with malignant STS, will be treated over a maximum recruitment period of three years. HIFU treatment will be carried out as a day case procedure, and patients will be expected to be discharged home the same day. The study is designed to generate evidence regarding safety and feasibility of HIFU for ablation of STS and intra-abdominal desmoids. In addition, the study is anticipated to provide information about the efficacy of HIFU against these tumour types which can help in the design of later phase studies. Short-term outcomes include feasibility, safety and the completeness of destruction of the tumour. Long-term outcomes include one-year survival, local recurrence and quality of life metrics (including pain scores). The study will also look at immunological response following ablation of STS using both blood and tumour samples pre- and post-HIFU ablation.

Conditions

Soft Tissue Sarcoma; Desmoid Tumors

Keywords

HIFU; Focused Ultrasound; Immunology

Outcome Measures

Primary Outcomes (4)

• Safety: Adverse events and serious adverse events deemed due to HIFU

  Adverse events and serious adverse events deemed due to HIFU recorded using Clavien-Dindo grading

  Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)

• Safety: Number of resectable STS participants converted to unresectable by HIFU

  Number of resectable STS participants converted to unresectable by HIFU

  Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)

• Safety: Number of limb salvageable STS participants converted to amputation by HIFU

  Number of limb salvageable STS participants converted to amputation by HIFU

  Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)

• Safety: Number of patients with intra-abdominal desmoid tumour requiring surgery due to complication

  Number of patients with intra-abdominal desmoid tumour requiring surgery due to complication

  Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)

Secondary Outcomes (8)

• Efficacy: Number of resectable STS participants with near pathological complete response

  Pathological response assessed within 2 months of surgery or post-HIFU biopsy

• Efficacy: Number of STS participants with non-perfused Volume Ratio (NPVR) Radiological Response

  NPVR endpoints assessed using pre-HIFU MRI vs. post-HIFU MRI at: 2-4 weeks (resectable or unresectable), 3-months (±1 month) (unresectable only) and 1-year (±1 month) (unresectable only)

• Efficacy: Number of STS participants with RECIST Partial Radiological Response

  RECIST endpoints assessed using pre-HIFU MRI vs. post-HIFU MRI at: 2-4 weeks (resectable or unresectable), 3-months (±1 month) (unresectable only) and 1-year (±1 month) (unresectable only)

• Efficacy: Number of STS participants with PERCIST Partial Metabolic Response

  PERCIST endpoints assessed using pre-HIFU MRI vs. post-HIFU PET-CT at: 2-4 weeks (resectable or unresectable), 3-months (±1 month) (unresectable only) and 1-year (±1 month) (unresectable only)

• Efficacy: Number of Desmoid tumour participants with Non-perfused Volume Ratio (NPVR) Radiological Response

  NPVR radiological endpoint assessed using pre- and 2-4 weeks post-HIFU MRI

Other Outcomes (4)

• Exploratory: Systemic immune effects of HIFU for STS

  Tissue samples from baseline (biopsy) and post-surgery stored and analysed with IHC within 6 months. Immune bloods taken at baseline and 2-4 weeks, 3 months, 6 months and 12 months post-HIFU

• Exploratory: Local immune effects of HIFU for STS

  Tissue samples from baseline (biopsy) and post-surgery stored and analysed with IHC within 6 months. Immune bloods taken at baseline and 2-4 weeks, 3 months, 6 months and 12 months post-HIFU

• Exploratory: Number of STS participants with local recurrence within one-year

  Within 13 months of HIFU

Study Arms (1)

HIFU Treatment of STS or Intra-abdominal Desmoid Tumour

EXPERIMENTAL

All participants receive HIFU to their target tumour, hence this is a single arm study with 4 recruitment pathways.

Device: High Intensity Focused Ultrasound Ablation; Diagnostic Test: Tumour Biopsy and Venous Blood Tests

Interventions

High Intensity Focused Ultrasound Ablation DEVICE

The focused ultrasound exposure will be performed using the Haifu® Model-JC200 Focused Ultrasound Tumour Therapeutic System at the Churchill Hospital site, CE-approved for tumour therapy (or subsequent CE-approved device upgrades by Haifu®), the device completely upgraded in 2025. The participant will be positioned over the therapeutic device and water bath used to transmit the focused ultrasound to the target tumour. No anaesthesia or any combination of local anaesthesia, nerve block, epidural, conscious sedation or general anaesthetic may be used, depending on anatomical location, size of tumour, preference of HIFU team, patient and anaesthetist and other patient factors. In therapy mode, the tumour volume is treated with focused ultrasound to ablate the tumour tissues to high temperatures (in excess of 60ºC) using focused ultrasound targeted from outside the body. Patients are typically discharged with 24 hours.

HIFU Treatment of STS or Intra-abdominal Desmoid Tumour

Tumour Biopsy and Venous Blood Tests DIAGNOSTIC_TEST

Where appropriate, participants are also encouraged to undergo a pre-HIFU (and in the case of unresectable STS, post-HIFU) ultrasound biopsy of the target tumour and additional blood tests to inform the immunological aspects of the study. Having the biopsy does not mandate enrolment on the trial, and patients will be free to leave the trial at any stage. The pre-HIFU (and post-HIFU) biopsies are altruistically encouraged but not absolutely essential to enrolment on the trial. Biopsies will be performed under ultrasound guidance by an experienced radiologist using local anaesthetic.

HIFU Treatment of STS or Intra-abdominal Desmoid Tumour

Eligibility Criteria

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

You may qualify if:

• \--------
• The participant is eligible for the study if they are:
• Willing and able to give informed consent for participation in the study.
• Aged 18 years or above.
• Diagnosed with histologically-confirmed and HIFU-targetable soft tissue sarcoma of several subtypes, including but not necessarily limited to:
• Malignant fibrous histiocytoma
• Undifferentiated (pleomorphic) sarcoma
• Fibrosarcoma and fibromyxoid sarcoma (fibroblastic sarcomas)
• Leiomyosarcoma
• Liposarcoma
• Malignant peripheral nerve sheath tumour
• Retroperitoneal sarcoma
• Rhabdomyosarcoma
• Synovial sarcoma
• Sacral chordoma (following amendment)

You may not qualify if:

• \--------
• The participant may not enter the study if ANY of the following apply:
• Diagnosed with histologically confirmed Osteosarcoma or Chordoma
• Diagnosed with histologically confirmed soft tissue sarcoma of the following subtypes:
• GIST
• Chondrosarcoma
• Kaposi's sarcoma
• Ewings sarcoma
• Giant cell tumour
• Angiosarcoma
• Pregnancy.
• Retroperitoneum
• Skull
• Neck
• Axilla

Sponsors & Collaborators

• Oxford Radiology Research Unit, Churchill Hospital, Oxford, UK: collaborator
• Oxford University Hospitals NHS Trust: lead
• Surgical Intervention Trials Unit, Oxford, UK: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Churchill Hospital

Oxford, Oxfordshire, United Kingdom

RECRUITING

Related Publications (21)

• Yu W, Tang L, Lin F, Jiang L, Shen Z. Significance of HIFU in local unresectable recurrence of soft tissue sarcoma, a single-center, respective, case series in China. Surg Oncol. 2019 Sep;30:117-121. doi: 10.1016/j.suronc.2019.06.004. Epub 2019 Jul 4.

  PMID: 31500773 BACKGROUND

• Gillies MJ, Lyon PC, Wu F, Leslie T, Chung DY, Gleeson F, Cranston D, Bojanic S. High-intensity focused ultrasonic ablation of sacral chordoma is feasible: a series of four cases and details of a national clinical trial. Br J Neurosurg. 2017 Aug;31(4):446-451. doi: 10.1080/02688697.2016.1267330. Epub 2016 Dec 12.

  PMID: 27936948 BACKGROUND

• Dangoor A, Seddon B, Gerrand C, Grimer R, Whelan J, Judson I. UK guidelines for the management of soft tissue sarcomas. Clin Sarcoma Res. 2016 Nov 15;6:20. doi: 10.1186/s13569-016-0060-4. eCollection 2016.

  PMID: 27891213 BACKGROUND

• Tsagozis P, Brosjo O, Skorpil M. Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival. Clin Sarcoma Res. 2018 Oct 5;8:19. doi: 10.1186/s13569-018-0106-x. eCollection 2018.

  PMID: 30323920 BACKGROUND

• Scipione R, Anzidei M, Bazzocchi A, Gagliardo C, Catalano C, Napoli A. HIFU for Bone Metastases and other Musculoskeletal Applications. Semin Intervent Radiol. 2018 Oct;35(4):261-267. doi: 10.1055/s-0038-1673363. Epub 2018 Nov 5.

  PMID: 30402009 BACKGROUND

• Illing RO, Kennedy JE, Wu F, ter Haar GR, Protheroe AS, Friend PJ, Gleeson FV, Cranston DW, Phillips RR, Middleton MR. The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population. Br J Cancer. 2005 Oct 17;93(8):890-5. doi: 10.1038/sj.bjc.6602803.

  PMID: 16189519 BACKGROUND

• Leslie TA, Kennedy JE, Illing RO, Ter Haar GR, Wu F, Phillips RR, Friend PJ, Roberts IS, Cranston DW, Middleton MR. High-intensity focused ultrasound ablation of liver tumours: can radiological assessment predict the histological response? Br J Radiol. 2008 Jul;81(967):564-71. doi: 10.1259/bjr/27118953.

  PMID: 18559903 BACKGROUND

• Lyon PC, Rai V, Price N, Shah A, Wu F, Cranston D. Ultrasound-Guided High Intensity Focused Ultrasound Ablation for Symptomatic Uterine Fibroids: Preliminary Clinical Experience. Ultraschall Med. 2020 Oct;41(5):550-556. doi: 10.1055/a-0891-0729. Epub 2019 Jun 25.

  PMID: 31238385 BACKGROUND

• Sturt NJ, Clark SK. Current ideas in desmoid tumours. Fam Cancer. 2006;5(3):275-85; discussion 287-8. doi: 10.1007/s10689-005-5675-1.

  PMID: 16998673 BACKGROUND

• Shi Y, Huang Y, Zhou M, Ying X, Hu X. High-intensity focused ultrasound treatment for intra-abdominal desmoid tumors: a report of four cases. J Med Ultrason (2001). 2016 Apr;43(2):279-84. doi: 10.1007/s10396-015-0682-9. Epub 2015 Oct 27.

  PMID: 27033872 BACKGROUND

• Ghanouni P, Dobrotwir A, Bazzocchi A, Bucknor M, Bitton R, Rosenberg J, Telischak K, Busacca M, Ferrari S, Albisinni U, Walters S, Gold G, Ganjoo K, Napoli A, Pauly KB, Avedian R. Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study. Eur Radiol. 2017 Feb;27(2):732-740. doi: 10.1007/s00330-016-4376-5. Epub 2016 May 5.

  PMID: 27147222 BACKGROUND

• Shim J, Staruch RM, Koral K, Xie XJ, Chopra R, Laetsch TW. Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics. Pediatr Blood Cancer. 2016 Oct;63(10):1753-60. doi: 10.1002/pbc.26079. Epub 2016 May 19.

  PMID: 27199087 BACKGROUND

• Leslie T, Ritchie R, Illing R, Ter Haar G, Phillips R, Middleton M, Bch B, Wu F, Cranston D. High-intensity focused ultrasound treatment of liver tumours: post-treatment MRI correlates well with intra-operative estimates of treatment volume. Br J Radiol. 2012 Oct;85(1018):1363-70. doi: 10.1259/bjr/56737365. Epub 2012 Jun 14.

  PMID: 22700259 BACKGROUND

• Lyon PC, Gray MD, Mannaris C, Folkes LK, Stratford M, Campo L, Chung DYF, Scott S, Anderson M, Goldin R, Carlisle R, Wu F, Middleton MR, Gleeson FV, Coussios CC. Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial. Lancet Oncol. 2018 Aug;19(8):1027-1039. doi: 10.1016/S1470-2045(18)30332-2. Epub 2018 Jul 11.

  PMID: 30001990 BACKGROUND

• Wu F, Wang ZB, Chen WZ, Wang W, Gui Y, Zhang M, Zheng G, Zhou Y, Xu G, Li M, Zhang C, Ye H, Feng R. Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. Ultrason Sonochem. 2004 May;11(3-4):149-54. doi: 10.1016/j.ultsonch.2004.01.011.

  PMID: 15081972 BACKGROUND

• Kennedy JE, Wu F, ter Haar GR, Gleeson FV, Phillips RR, Middleton MR, Cranston D. High-intensity focused ultrasound for the treatment of liver tumours. Ultrasonics. 2004 Apr;42(1-9):931-5. doi: 10.1016/j.ultras.2004.01.089.

  PMID: 15047409 BACKGROUND

• Gray MD, Lyon PC, Mannaris C, Folkes LK, Stratford M, Campo L, Chung DYF, Scott S, Anderson M, Goldin R, Carlisle R, Wu F, Middleton MR, Gleeson FV, Coussios CC. Focused Ultrasound Hyperthermia for Targeted Drug Release from Thermosensitive Liposomes: Results from a Phase I Trial. Radiology. 2019 Apr;291(1):232-238. doi: 10.1148/radiol.2018181445. Epub 2019 Jan 15.

  PMID: 30644817 BACKGROUND

• Chetan MR, Lyon PC, Wu F, Phillips R, Cranston D, Gillies MJ, Bojanic S. Role of diffusion-weighted imaging in monitoring treatment response following high-intensity focused ultrasound ablation of recurrent sacral chordoma. Radiol Case Rep. 2019 Aug 1;14(10):1197-1201. doi: 10.1016/j.radcr.2019.07.004. eCollection 2019 Oct.

  PMID: 31428215 BACKGROUND

• Schmidt GP, Reiser MF, Baur-Melnyk A. Whole-body MRI for the staging and follow-up of patients with metastasis. Eur J Radiol. 2009 Jun;70(3):393-400. doi: 10.1016/j.ejrad.2009.03.045. Epub 2009 May 19.

  PMID: 19457631 BACKGROUND

• Wu F. Heat-Based Tumor Ablation: Role of the Immune Response. Adv Exp Med Biol. 2016;880:131-53. doi: 10.1007/978-3-319-22536-4_8.

  PMID: 26486336 BACKGROUND

• Wu F, Wang ZB, Lu P, Xu ZL, Chen WZ, Zhu H, Jin CB. Activated anti-tumor immunity in cancer patients after high intensity focused ultrasound ablation. Ultrasound Med Biol. 2004 Sep;30(9):1217-22. doi: 10.1016/j.ultrasmedbio.2004.08.003.

  PMID: 15550325 BACKGROUND

Related Links

• Sarcoma UK Webpage

MeSH Terms

Conditions

Sarcoma; Desmoid Tumors

Interventions

High-Intensity Focused Ultrasound Ablation

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Ultrasonic Therapy; Diathermy; Hyperthermia, Induced; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Paul C Lyon, FRCR, DPhil

  Oxford University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul C Lyon, FRCR, DPhil

CONTACT

0300 304 7777; sarcablate@nds.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Model Details: No randomisation. Four recruitment cohorts, patients with: 1. Soft tissue sarcoma 1-5cm for resection 2. Soft tissue sarcoma \>1cm with infield recurrence for resection 3. Soft tissue sarcoma unsuitable for resection or further chemo- or radiotherapy 4. Small (1-8 cm) symptomatic desmoid tumour unsuitable for surgery

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: November 8, 2021
• Study Start: December 10, 2021
• Primary Completion (Estimated): December 10, 2026
• Study Completion (Estimated): December 10, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)