Clinical trial NCT04310410: Feasibility of Combined Focused Ultrasound and Radiotherapy Treatment in Patients With Painful Bone Metastasis
Official title: Feasibility of Combined Focused Ultrasound and Radiotherapy Treatment in Patients With Painful Bone Metastasis - the PRE-FURTHER Study -
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bone Metastases
Bone Neoplasm
Bone Lesion
Bone Cancer
Pain
Cancer Induced Bone Pain
Radiation Toxicity
Quality of Life
Tumor
Neoplasm Metastasis
Keywords: Bone metastases
Cancer Induced Bone Pain
Pain palliation
Radiotherapy
Radiation oncology
MR-HIFU
MRI-guided high intensity focused ultrasound
Focused ultrasound
HIFU
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Isala
First posted: 2020-03-17
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Prospective case series (n = 6 - 10), stage I and IIA study according to the Innovation, Development, Evaluation, Assessment and Long term evaluation (IDEAL) recommendations. The study will be performed in male and female adult (≥ 18 years) cancer patients capable of giving informed consent and referred for EBRT of painful bone metastases (Numerical Rating Scale (NRS) ≥ 4).
Primary purpose: OTHER

Brief summary: The PRE-FURTHER study aims to evaluate the feasibility of the combined treatment with radiotherapy and focussed ultrasound for pain palliation in patients with painful bone metastases, and to optimize the combined treatment logistics. Six to ten patients will be included according to in- and exclusion criteria.

Detailed description: Rationale: Metastatic bone pain strongly interferes with quality of life and daily functioning of patients with advanced cancer. Pain palliation may be improved by including magnetic resonance image guided high intensity focused ultrasound (MR-HIFU) in addition to External Beam Radiotherapy (EBRT). For this purpose, feasibility and optimal logistics of the combined treatment need to be evaluated.

Objective: The PRE-FURTHER project aims to evaluate the feasibility of the combined EBRT and MR-HIFU treatment for relief of metastatic bone pain, and to optimize the combined treatment logistics.

Study design: The PRE-FURTHER study is a prospective case series, stage I and IIA study according to the Innovation, Development, Evaluation, Assessment and Long term evaluation (IDEAL) recommendations. 6-10 patients will receive MR-HIFU treatment following standard EBRT.

Endpoints: The main outcome of this study is the feasibility of the procedure, in terms of planability as well as patient-tolerability of the combined treatment within a short time frame (3 hours - 4 days interval). In addition, pain relief and safety of the combined procedure will be monitored.

Eligibility criteria: Inclusion Criteria:

* Men and women with age ≥ 18 years
* Patient capable of giving informed consent and able to attend study visits
* Uncomplicated painful bone metastases
* Weight \<140kg and able to fit in the MRI gantry
* Radiologic evidence of bone metastases from any solid tumor
* Pain is localized to the targeted area, or is likely to be referred pain arising from the targeted area
* Pain related to the target lesion is refractory to less invasive treatments for pain relief
* Multiple metastatic lesions, with one predominantly painful lesion (\>=2 points higher pain score than other lesions). The lesion should be clearly distinguishable from other painful lesions.
* Device accessible tumors: extremities (excluding joints), pelvis, shoulders, posterior vertebral spine below L5, in selected cases ribs and sternum
* Target lesion maximum dimension ≤ 8cm
* Intended target volume visible by non-contrast MR imaging
* Distance between target and skin ≥ 1cm
* Numeric Rating Scale (NRS) score \>= 4 or equivalent
* Life expectancy \>3 months

Exclusion Criteria:

* Planned treatment lesion is a primary bone tumor or due to lymphoma, multiple myeloma, or leukemia.
* Communication barrier present
* Patient enrolled in another clinical study related to bone metastases treatment or pain relief treatment
* Unable to tolerate required stationary position during treatment despite adequate pain medication
* Need for surgery
* Pregnant woman
* Pain related to target lesion is predominantly due to fracture or impending fracture
* Pain related to target lesion is due to involvement of a neighboring major nerve by the metastatic tumor (cord or nerve compression)
* Target \< 3cm from bladder / bowel / nerve along the beam path and \< 1cm in the plane orthogonal to the beam
* Target in contact with hollow viscera
* Target located in skull, joints, ribs (when HIFU beam overlapping with lung), spine (excluding sacrum which is allowed) or in most cases sternum
* Internal or external fixation device along the proposed HIFU beam path or at the target
* MRI contraindicated (e.g. paramagnetic implants, pacemaker, claustrophobia)
* MRI contrast agent contraindicated (e.g. previous anaphylaxis or Glomerular Filtration Rate \< 20 ml/min/1.73m2)
* Sedation contraindicated
* Previous surgery or minimally invasive treatment at targeted site within the last three months
* Clinically relevant medical history or abnormal physical findings that could interfere with the safety of the participant as judged by the treating physician or investigator
* Karnofsky performance score (KPS) \< 60%
* Oligometastatic disease planned for curative treatment
* Indication for stereotactic radiotherapy (e.g. patients with radioresistant histology such as renal cell, melanoma, sarcoma metastases)
* History of photodermatoses (of the skin overlying the target area)
* Need for remineralisation

Primary outcomes:
measure: Feasibility of combined treatment with EBRT and MR-HIFU - Patient tolerance: questionnaire
timeFrame: 4 weeks
measure: Feasibility of combined treatment with EBRT and MR-HIFU - hospital logistics
timeFrame: 4 weeks
Secondary outcomes:
measure: Patient reported pain scores.
timeFrame: at 3 days, and at 1, 2, 3 and 4 weeks
measure: (Serious) adverse events
timeFrame: at 3 days, and at 1, 2, 3 and 4 weeks
Other outcomes:
Locations:
city: Zwolle
country: Netherlands
facility: Isala Klinieken Zwolle
state: Overijsel
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Helena M Verkooijen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: