Feasibility of Combined Focused Ultrasound and Radiotherapy Treatment in Patients With Painful Bone Metastasis (PRE-FURTHER)

Feasibility of Combined Focused Ultrasound and Radiotherapy Treatment in Patients With Painful Bone Metastasis - the PRE-FURTHER Study -

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.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Pain; Neoplasm Metastasis; Bone Cancer; Bone Metastases; Tumor; Radiation Toxicity; Bone Neoplasm; Bone Lesion; Cancer Induced Bone Pain
• Intervention / Treatment: Combination product: combined radiotherapy and MR-HIFU

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3508GA
    • University Medical Center Utrecht
  • Overijsel
    • Zwolle, Overijsel, Netherlands, 8025 AB
      • Isala Klinieken Zwolle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combined Focused Ultrasound and Radiotherapy; Combination of focused ultrasound and external beam radiotherapy

Combination product: combined radiotherapy and MR-HIFU; Following standard EBRT (single or multiple fraction), patients will receive one MR-HIFU treatment with the Profound Sonalleve MR-HIFU device on the most painful of their bone metastases. This treatment will take place in a short time frame of 3 hours to maximum 4 days. Patients will be followed up until 4 weeks after treatment. During follow-up they will be phoned around day 3, 7, 14, 21 and 28 to retrieve pain scores, pain medication and (serious) adverse events. At day 3 the patient's experience with the combined treatment will also be inquired.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of combined treatment with EBRT and MR-HIFU - Patient tolerance: questionnaire	The main outcome of this study is the feasibility of the combined procedure in terms of patient tolerance and hospital logistics. Patient tolerance will be assessed using a Patient Reported Experience Measure questionnaire.	4 weeks
Feasibility of combined treatment with EBRT and MR-HIFU - hospital logistics	The main outcome of this study is the feasibility of the combined procedure in terms of patient tolerance and hospital logistics. Hospital logistics will be assessed by analysing comments of the treating physicians and research staff on the problems that occurred during treatment planning, and whether extra hospital visits that were needed.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported pain scores.	Patient reported pain scores will be based on a Numeric Rating Scale (from 0 to 10 with 0 being no pain and 10 being the worst pain imaginable) from the Brief Pain Inventory (BPI) questionnaire [Cleeland 1994].	at 3 days, and at 1, 2, 3 and 4 weeks
(Serious) adverse events	Toxicity/safety of the combined treatment will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	at 3 days, and at 1, 2, 3 and 4 weeks

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Isala
• Investigators: Principal Investigator: Helena M Verkooijen, MD, PhD, UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2019
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Radiotherapy; Focused ultrasound; Bone metastases; HIFU; Radiation oncology; MR-HIFU; Cancer Induced Bone Pain; Pain palliation; MRI-guided high intensity focused ultrasound
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Hematologic Diseases; Musculoskeletal Diseases; Neoplastic Processes; Bone Diseases; Neoplasms; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases; Neoplasms, Second Primary
• Other Study ID Numbers: NL68441.041.19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No