HIFU Ablation of Soft Tissue Sarcoma
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorOxford University Hospitals NHS Trust
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Malignant fibrous histiocytoma
Undifferentiated (pleomorphic) sarcoma
Fibrosarcoma and fibromyxoid sarcoma (fibroblastic sarcomas)
Leiomyosarcoma
Disqualifiers
GIST
Chondrosarcoma
Kaposi's sarcoma
Ewings sarcoma
Trial design
Design model
Single group
Treatments tested in this trial
High Intensity Focused Ultrasound Ablation
DeviceThe 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.
Tumour Biopsy and Venous Blood Tests
Diagnostic testWhere 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.
Treatment groups
10 Participants
are divided into 1 treatment groupGroup A: HIFU Treatment of STS or Intra-abdominal Desmoid TumourExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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
Time frame
Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)2
Safety: Number of resectable STS participants converted to unresectable by HIFU
Number of resectable STS participants converted to unresectable by HIFU
Time frame
Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)3
Safety: Number of limb salvageable STS participants converted to amputation by HIFU
Number of limb salvageable STS participants converted to amputation by HIFU
Time frame
Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)4
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
Time frame
Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)Secondary outcomes
1
Efficacy: Number of resectable STS participants with near pathological complete response
Near pathological complete response (≥95% necrosis) in ≥25% of resectable STS participants post-HIFU
Time frame
Pathological response assessed within 2 months of surgery or post-HIFU biopsy2
Efficacy: Number of STS participants with non-perfused Volume Ratio (NPVR) Radiological Response
Non-perfused volume ratio (NPVR) ≥75% on MRI in ≥25% of all STS participants having MRI post-HIFU
Time frame
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)3
Efficacy: Number of STS participants with RECIST Partial Radiological Response
RECIST partial response in the target tumour alone in ≥25% of unresectable STS participants having MRI post-HIFU
Time frame
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)4
Efficacy: Number of STS participants with PERCIST Partial Metabolic Response
PERCIST partial metabolic response in the target tumour alone in ≥25% of all STS participants having PET-CT post-HIFU
Time frame
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)Other outcomes
1
Exploratory: Systemic immune effects of HIFU for STS
To measure the immunological effects of HIFU treatment of STS by immunohistochemistry (IHC) using tumour samples post-HIFU relative to baseline
Time frame
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-HIFU2
Exploratory: Local immune effects of HIFU for STS
To measure the immunological effects of HIFU treatment of STS by immune blood markers using venous blood samples post-HIFU relative to baseline
Time frame
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-HIFU3
Exploratory: Number of STS participants with local recurrence within one-year
One-year local recurrence endpoint assessed using available imaging (CT, MRI, PET-CT)
Time frame
Within 13 months of HIFU4
Exploratory: Number of STS participants with survival for over one-year
One-year survival endpoint assessed using available clinical information
Time frame
Within 12 months of HIFUSponsors and contacts
Click on the lead sponsor to view all of their trials.
Oxford University Hospitals NHS Trust
Lead sponsor
Surgical Intervention Trials Unit, Oxford, UK
Collaborator
National Institute for Health Research, United Kingdom
Collaborator
Oxford Radiology Research Unit, Churchill Hospital, Oxford, UK
Collaborator
Source ClinicalTrials.gov