A Pilot Study in High Intensity Focused Ultrasound Ablation of Soft Tissue Sarcoma and Small Symptomatic Desmoid Tumours
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Safety: Number of limb salvageable STS participants converted to amputation by HIFU
研究概览
简要总结
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.
详细描述
Tissues that can be affected by soft tissue sarcomas include fat, muscle, blood vessels, nerves, deep skin tissues, tendons and ligaments. Sarcoma accounts for 1% of all cancer diagnoses; around 3,300 people are diagnosed with soft tissue sarcoma (STS) each year in the UK. The incidence of STS is unusual for cancer in that a relatively large proportion can occur in children and young adults, with 9% of cases in the under 30-year group and only 43% of cases in the 65 and over group. Whilst STS is rare, it remains a significant cause of morbidity and mortality. Prognosis is typically poor, with a five-year overall survival of approximately 54%.
The Oxford Bone and Soft Tissue Tumour Service at the Nuffield Orthopaedic Centre, Oxford, is a nationally approved tertiary referral centre for the treatment of soft tissue and primary bone sarcomas, receiving 400 new patient referrals annually. These patients are currently treated via a multidisciplinary approach involving expert radiologists, surgeons, clinical oncologists and histopathologists.
At our centre, patients with smaller (<5cm) STS proceed directly to surgical resection; this provides a low-risk opportunity to evaluate safety, feasibility and efficacy of novel pre-operative non-ionising ablative technologies, such as High Intensity Focused Ultrasound (HIFU). Patients with larger (>5cm) resectable STS currently receive neoadjuvant radiotherapy within six weeks of surgery, in line with national guidelines (Dangoor, 2016). Upon recurrence within the radiotherapy field (in-field recurrence), radiotherapy has high morbidity, including complications such as poor wound healing and infection (Tsagozis, 2018), and is not indicated prior to further surgical resection. Thus, in resectable cases of in-field recurrence, there is further opportunity to evaluate non-invasive HIFU, anticipated to both reduce tumour size and tumour vascularity, facilitating subsequent surgical resection. Furthermore, recurrent STS or metastatic STS not suitable for surgery have limited treatment options, and if not suitable for further chemo- or radio-therapy, HIFU may provide an alternative treatment option before palliation.
HIFU is a versatile treatment modality capable of destruction of tumours by focusing ultrasound waves from outside the body, usually through the medium of water, to cause ablation at a precise anatomical location.
It has demonstrated an impressive safety profile by virtue of being both non-invasive and lacking radiation, leading to FDA approvals for several indications including pain relief in bone metastases (Scipione, 2018) and uterine fibroids. Previous studies using an ultrasound-guided therapeutic device in China have demonstrated that HIFU is a successful treatment modality for soft tissue sarcoma (Yu, 2019), but this treatment has currently not been widely investigated within the UK's health care setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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:
- •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).
- •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
- •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.
研究组 & 干预措施
HIFU Treatment of STS or Intra-abdominal Desmoid Tumour
All participants receive HIFU to their target tumour, hence this is a single arm study with 4 recruitment pathways.
干预措施: High Intensity Focused Ultrasound Ablation (Device)
HIFU Treatment of STS or Intra-abdominal Desmoid Tumour
All participants receive HIFU to their target tumour, hence this is a single arm study with 4 recruitment pathways.
干预措施: Tumour Biopsy and Venous Blood Tests (Diagnostic Test)
结局指标
主要结局
Safety: Number of limb salvageable STS participants converted to amputation by HIFU
时间窗: Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)
Number of limb salvageable STS participants converted to amputation by HIFU
Safety: Number of patients with intra-abdominal desmoid tumour requiring surgery due to complication
时间窗: Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)
Number of patients with intra-abdominal desmoid tumour requiring surgery due to complication
Safety: Number of resectable STS participants converted to unresectable by HIFU
时间窗: Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)
Number of resectable STS participants converted to unresectable by HIFU
Safety: Adverse events and serious adverse events deemed due to HIFU
时间窗: Adverse events endpoint assessed for up to 30 days post-HIFU (or up to point of surgery if sooner)
Adverse events and serious adverse events deemed due to HIFU recorded using Clavien-Dindo grading
次要结局
- 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 RECIST Partial Radiological Response(RECIST radiological endpoint assessed using 1-year post-HIFU MRI)
- 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 Desmoid tumour participants with Non-perfused Volume Ratio (NPVR) Radiological Response(NPVR radiological endpoint assessed using pre- and 2-4 weeks post-HIFU MRI)
- Efficacy: Number of desmoid tumour and unresectable STS participants with change in Pain Score assessed by Brief Pain Inventory post-HIFU relative to baseline(Pain score and quality of life endpoints assessed at baseline, 2-4 weeks and 3, 6 and 12 months post-HIFU (±1 month))
- Efficacy: Number of desmoid tumour and unresectable STS participants with change in Quality of Life score assessed by EORTC QLQ-C30(Pain score and quality of life endpoints assessed at baseline, 2-4 weeks and 3, 6 and 12 months post-HIFU (±1 month))
研究者
Paul Lyon
Primary Investigator
Oxford University Hospitals NHS Trust