Focused Ultrasound and RadioTHERapy for Noninvasive Palliative Pain Treatment in Patients With Bone Metastases (FURTHER)

February 5, 2024 updated by: Helena M Verkooijen, UMC Utrecht
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Main study endpoints: Primary outcome of the study will be pain response at 14 days after the first day of treatment. Secondary outcomes include pain response at 14 days after inclusion, and pain scores, toxicity, adverse events, quality of life and survival in the first 6 months after treatment, and cost-effectiveness of the treatments.

Study Type

Interventional

Enrollment (Estimated)

216

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: External Beam Radiotherapy
In the control arm, patients will undergo standard radiotherapy for painful bone metastases.The radiation schedule is at the discretion of the treating radiation oncologist.
Radiation: External beam radiotherapy
The current standard of care for patients with uncomplicated painful bone metastases is palliative locoregional external beam radiotherapy, often in combination with systemic therapy and analgesics.
Experimental: MR-HIFU
In the intervention arm, patients will be offered MR-HIFU treatment instead of standard radiotherapy. Treatment will be given following the international guidelines for MR-HIFU.
Procedure: MR-HIFU
MR-HIFU is a non-invasive treatment modality that delivers acoustic energy to heat tissue to ablative temperatures of more than 60°C. The combination of focused ultrasound with magnetic resonance imaging (MRI) enables physicians to perform localized tumor tissue ablation, with real-time temperature monitoring using magnetic resonance (MR) thermometry.
Other Names:
  • MRgFUS
  • MR guided High Intensity Focused Ultrasound
Experimental: Combination EBRT + MR-HIFU
In the combination arm, patients will undergo standard radiotherapy followed by MR-HIFU in a short timeframe.
Radiation: External beam radiotherapy
The current standard of care for patients with uncomplicated painful bone metastases is palliative locoregional external beam radiotherapy, often in combination with systemic therapy and analgesics.
Procedure: MR-HIFU
MR-HIFU is a non-invasive treatment modality that delivers acoustic energy to heat tissue to ablative temperatures of more than 60°C. The combination of focused ultrasound with magnetic resonance imaging (MRI) enables physicians to perform localized tumor tissue ablation, with real-time temperature monitoring using magnetic resonance (MR) thermometry.
Other Names:
  • MRgFUS
  • MR guided High Intensity Focused Ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain response - 14 days after completion of treatment
Time Frame: 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.
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain response - 14 days after inclusion
Time Frame: 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). This endpoint 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.
14 days
Patient reported pain scores - patient pain diary
Time Frame: 21 days
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). This will be assessed using a daily patient pain diary during the first 21 days after completion of treatment.
21 days
Patient reported pain scores - BPI
Time Frame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
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). This will be assessed using the Brief Pain Inventory (BPI) questionnaire at 7 time points during the total follow up of 6 months.
on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
Physician reported toxicity - CTCAE 5.0
Time Frame: at 3 days, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
Assessed in seven telephone calls during the first six months following completion of treatment according to the Common Terminology Criteria for Adverse Events (CTCAE) version 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
Time Frame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
During the follow up time of 6 months, patients will receive the EORTC BM22 quality of life questionnaire at baseline, one, two, four and six weeks, and three and six months following completion of treatment.
on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
Patient reported quality of life - EORTC C15-PAL
Time Frame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
During the follow up time of 6 months, patients will receive the EORTC C15-PAL quality of life questionnaire at baseline, one, two, four and six weeks, and three and six months following completion of treatment.
on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
Patient reported quality of life - EQ-5D-5L
Time Frame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
During the follow up time of 6 months, patients will receive the EQ-5D-5L quality of life questionnaire at baseline, one, two, four and six weeks, and three and six months following completion of treatment.
on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
Patient reported quality of life - PGIC
Time Frame: at 1, 2, 4 and 6 weeks, and at 3 and 6 months
During the follow up time of 6 months, patients will receive the Patient Global Impression of Change scale (a 7 point likert scale about overall improvement after treatment) at one, two, four and six weeks, and three and six months following completion of treatment.
at 1, 2, 4 and 6 weeks, and at 3 and 6 months
Patient reported quality of life - HADS
Time Frame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months

During the follow up time of 6 months, patients will receive the Hospital Anxiety and Depression Scale (HADS) questionnaire at one, two, four and six weeks, and three and six months following completion of treatment.

Assessed among patients, patients' partners and caregivers by the Hospital Anxiety and Depression Scale (HADS) at baseline, two and four weeks, and three and six months fol-lowing completion of treatment.
on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
Local tumour control
Time Frame: 3 and 6 months
Assessed using CT and/or MRI imaging at patient discretion at three and/or six months after completion of treatment.
3 and 6 months
Cost-effectiveness of the treatment
Time Frame: 6 months
A hypothetical diagnosis related group (DRG) will be calculated from the perspective of the statutory health insurance (SHI).
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Collaborators

Turku University Hospital
University of Bologna
University of Roma La Sapienza
Istituto Ortopedico Rizzoli
Isala
Universitätsklinikum Köln

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2020

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

March 5, 2020

First Submitted That Met QC Criteria

March 12, 2020

First Posted (Actual)

March 13, 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

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL71303.041.19

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Quality of Life

Clinical Trials on External beam radiotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kazakhstan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe