HIFU Ablation of Soft Tissue Sarcoma
A Pilot Study in High Intensity Focused Ultrasound Ablation of Soft Tissue Sarcoma and Small Symptomatic Desmoid Tumours
Oxford University Hospitals NHS Trust
10 participants
Dec 10, 2021
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria25
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- 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)
- Desmoid tumours (intra- or extra-abdominal, following amendment)
- Have at least one of the following:
- Untreated or recurrent primary resectable STS tumour 1-5cm diameter, targetable by HIFU
- Infield recurrent primary resectable STS tumour of \>1cm diameter, targetable by HIFU
- Primary or metastatic STS unsuitable for resection or further chemo- or radiotherapy, targetable by HIFU
- Small (1-8cm) symptomatic intra- or extra-abdominal desmoid tumour, targetable by HIFU, which is not indicated for surgery (or patient has declined surgery)
- Have life expectancy of over 12 months and a World Health Organisation (WHO) performance status of less than or equal to 1.
- Be able to attend Churchill Hospital and Nuffield Orthopaedic Center, Oxford, potentially for multiple visits, and thus be based in the UK.
- Willing to allow his or her GP and Consultant to be notified of participation in the study.
- Able and willing to give written informed consent, indicating that they are aware of the investigational nature of this study and potential risks, and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.
Exclusion Criteria33
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- 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
- Active medical or psychological illness that would render the patient unsuitable for the interventions required for the study (exclusion at the discretion of the investigator).
- Pregnancy.
- Ulceration / skin breakdown / erythema overlying the target tumour site due to tumour invasion (exclusion at the discretion of the investigator).
- Significant radiation skin damage overlying the target tumour site (exclusion at the discretion of the investigator).
- Impractical anatomical locations for HIFU targeting (using JC200 treatment device) (exclusion at the discretion of the investigator):
- Retroperitoneum
- Skull
- Neck
- Axilla
- Foot
- Unfavourable imaging features on previously acquired cross-sectional imaging, including:
- Tumour within 1cm of the skin surface
- Interposition (or close proximity) of a gas-containing structure between tumour and skin such as fixed (retroperitoneal) bowel or lung
- Interposition of a continuous ossified bone between tumour and skin, such as coverage by pelvis or scapula
- Tumour margin close (\<1.5cm) or encasing major neurovascular bundles (such as the sciatic nerve)
- Tumour margin close (\<1.5 cm) to critical visceral structures (e.g. bladder or bowel)
- Recent radiotherapy (under 6 months) to the target tumour site.
- Recent surgery (under 6 weeks) to the target tumour site.
- Have any known allergic reactions to intravenous imaging agents to be used in this study (exclusion at the discretion of the investigator).
- Have contraindication(s) or intolerance to MRI (exclusion at the discretion of the investigator).
- Current involvement in phase 1 studies.
- Soft tissue sarcoma participants: Use of chemotherapy or of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the intervention.
- Desmoid participants: hormonal medication including the contraceptive pill or tamoxifen, or being treated with imatinib.
Interventions
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.
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.
Locations(1)
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NCT05111964