Focused Ultrasound and RadioTHERapy for Noninvasive Palliative Pain Treatment in Patients With Bone Metastases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- UMC Utrecht
- 入组人数
- 216
- 试验地点
- 7
- 主要终点
- Pain response - 14 days after completion of treatment
研究概览
简要总结
The FURTHER study aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU (alone or in combination with EBRT) compared to EBRT alone, the standard-of-care, as a palliative treatment option to relieve CIBP. The FURTHER study consists of a multicenter, three-armed randomized controlled trial (FURTHER RCT) and a patient registry arm (FURTHER Registry), which will be performed in six hospitals in four European countries.
详细描述
Rationale: Cancer induced bone pain (CIBP) as a result of bone metastases strongly interferes with quality of life and daily functioning of patients with advanced cancer. The current standard of care for patients with painful bone metastasis includes palliative external beam radiotherapy (EBRT). While EBRT is a well-established treatment option, it takes up to 4-6 weeks for EBRT to induce optimal pain relief, and 30-40% of patients do not respond to EBRT. Pain palliation may be improved by including magnetic resonance image guided high intensity focused ultrasound (MR-HIFU) as alternative or in addition to EBRT.
Objective: The FURTHER study aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU (alone or in combination with EBRT), as a palliative treatment option to relieve CIBP.
Study design: The FURTHER study consists of a prospective, multicenter, three-armed randomized controlled trial (FURTHER RCT) and a patient registry arm (FURTHER Registry), performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. The UMC Utrecht is coordinating center. Within the FURTHER RCT, a total of 216 patients with painful bone metastases will be included. These patients will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or EBRT followed by MR-HIFU. In the Netherlands, we expect to enroll a minimum of 70 patients, and a maximum of 120 patients in three Dutch study sites. Within the FURTHER Registry, data of around 60-90 patients will be captured.
Study population: The study will be performed in male and female adult (≥ 18 years) cancer patients capable of giving informed consent having painful non-spinal bone metastases (pain score on Numerical Rating Scale (NRS) ≥ 4).
Intervention: The intervention under study is MR-HIFU alone or in combination with EBRT. The intervention is aimed at rapid and persistent relief of CIBP. In the FURTHER RCT, the intervention will be compared to standard treatment EBRT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patient capable of giving informed consent
- •Age ≥ 18 years
- •Painful metastatic bone lesion (NRS > 2)
- •Patient-localised pain with a distinct pathological substrate on recent CT/MRI
- •Target lesion location is sufficiently accessible for MR-HIFU to expect clinical response, as judged by the (intervention) radiologist
- •Participant has a reasonable performance score (KPS ≥ 50% or Zubrod/ECOG/WHO < 3)
- •Life expectancy ≥ 3 months
排除标准
- •Participant is not able to fit in the MR gantry
- •Need for surgery of targeted location due to (impending) pathological fracture
- •Unavoidable critical structures or dense tissues in target area
- •Contra-indications for MRI or sedation/anesthesia
- •Clinically relevant medical history or physical findings that could interfere with the patient's safety as judged by the treating physician
- •Participant enrolled in another clinical interventional study related to bone metastases treatment or pain relief treatment
- •All patients meeting the FURTHER in- and exclusion criteria as described above will be included in this study, either in the FURTHER RCT or FUTHER Registry. The following inclusion criteria are used to decide upon the arm patients will participate in. If patients meet all of the following RCT inclusion criteria, they will be asked to participate in the FURTHER RCT. Alternatively, patients who do not meet one or more of these criteria will be asked to participate in the FURTHER Registry.
- •Painful bone lesion (NRS ≥ 4)
- •Indication for EBRT treatment of a bone lesion
- •Exclusively palliative intention of EBRT treatment plan
- •No previous surgery on the target location
- •No neurological symptoms due to nerve involvement of target lesion
- •No (impending) pathological fracture)
- •EBRT replacable by MR-HIFU based on medical history or phyiscal findings judged by multidisciplinary team
- •Target lesion location is completely accessible for MR-HIFU
结局指标
主要结局
Pain response - 14 days after completion of treatment
时间窗: 14 days
Patient reported pain response will be based on a Numeric Rating Scale (from 0 to 10 with 0 being no pain and 10 being the worst pain imaginable) and the pain severity index calculated from the Brief Pain Inventory (BPI) questionnaire \[Cleeland 1994\]. In addition, analgesic and anti-neuropathic drug use is recorded, and all opioid analgesics are expressed as the oral equivalent daily morphine use (OMED). The primary endpoint of the RCT will follow the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone metastases (Chow 2012). Patients will be categorized as responders when a complete or partial pain response is achieved. All other patients will be categorized as non-responders.
次要结局
- Pain response - 14 days after inclusion(14 days)
- Patient reported pain scores - patient pain diary(21 days)
- Physician reported toxicity - CTCAE 5.0(at 3 days, at 1, 2, 4 and 6 weeks, and at 3 and 6 months)
- Patient reported quality of life - EORTC BM22(on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months)
- Patient reported pain scores - BPI(on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months)
- Patient reported quality of life - PGIC(at 1, 2, 4 and 6 weeks, and at 3 and 6 months)
- Local tumour control(3 and 6 months)
- Patient reported quality of life - EORTC C15-PAL(on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months)
- Patient reported quality of life - EQ-5D-5L(on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months)
- Patient reported quality of life - HADS(on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months)
- Cost-effectiveness of the treatment(6 months)
研究者
Helena M Verkooijen
Principal Investigator
UMC Utrecht