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

NCT ID: NCT04307914

Last Updated: 2024-02-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

216 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-10

Study Completion Date

2026-06-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Bone Metastases Bone Neoplasm Bone Lesion Bone Cancer Pain Cancer Induced Bone Pain Quality of Life Tumor Neoplasm Metastasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or EBRT followed by MR-HIFU. In addition, data of around 60-90 patients will be captured within the FURTHER Registry arm.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

External beam radiotherapy

Intervention Type RADIATION

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.

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.

Group Type EXPERIMENTAL

MR-HIFU

Intervention Type PROCEDURE

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.

Combination EBRT + MR-HIFU

In the combination arm, patients will undergo standard radiotherapy followed by MR-HIFU in a short timeframe.

Group Type EXPERIMENTAL

External beam radiotherapy

Intervention Type RADIATION

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.

MR-HIFU

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type RADIATION

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.

Intervention Type PROCEDURE

Other Intervention Names

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MRgFUS MR guided High Intensity Focused Ultrasound

Eligibility Criteria

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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


* 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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Turku University Hospital

OTHER_GOV

Sponsor Role collaborator

Universitätsklinikum Köln

OTHER

Sponsor Role collaborator

University of Roma La Sapienza

OTHER

Sponsor Role collaborator

Istituto Ortopedico Rizzoli

OTHER

Sponsor Role collaborator

University of Bologna

OTHER

Sponsor Role collaborator

Isala

OTHER

Sponsor Role collaborator

UMC Utrecht

OTHER

Sponsor Role lead

Responsible Party

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Helena M Verkooijen

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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TUCH Turku

Turku, , Finland

Site Status RECRUITING

University Hospital Cologne

Cologne, , Germany

Site Status RECRUITING

IOR

Bologna, , Italy

Site Status RECRUITING

CSSP

Roma, , Italy

Site Status RECRUITING

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status RECRUITING

Isala Klinieken Zwolle

Zwolle, , Netherlands

Site Status RECRUITING

Countries

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Finland Germany Italy Netherlands

Central Contacts

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Renée Hovenier, MSc

Role: CONTACT

+31 6 5017 78 43

Helena M Verkooijen, MD, PhD

Role: CONTACT

+31 88 75 595 75

Facility Contacts

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Mira Huhtala

Role: primary

Heikki Minn

Role: backup

Sin Yuin Yeo

Role: primary

Holger Gruell

Role: backup

Alberto Bazzocchi

Role: primary

Milly Buwenge

Role: backup

Alessandro Napoli

Role: primary

Francesca de Felice

Role: backup

Helena M Verkooijen, MD, PhD

Role: primary

Renée Hovenier, MSc

Role: backup

Jorik Slotman

Role: primary

+31 38 424 44 92

Martijn Boomsma

Role: backup

+31 38 424 28 82

References

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Slotman DJ, Bartels MMTJ, Ferrer CJ, Bos C, Bartels LW, Boomsma MF, Phernambucq ECJ, Nijholt IM, Morganti AG, Siepe G, Buwenge M, Grull H, Bratke G, Yeo SY, Blanco Sequeiros R, Minn H, Huhtala M, Napoli A, De Felice F, Catalano C, Bazzocchi A, Gasperini C, Campanacci L, Simoes Correa Galendi J, Muller D, Braat MNGJA, Moonen C, Verkooijen HM; FURTHER consortium. Focused Ultrasound and RadioTHERapy for non-invasive palliative pain treatment in patients with bone metastasis: a study protocol for the three armed randomized controlled FURTHER trial. Trials. 2022 Dec 29;23(1):1061. doi: 10.1186/s13063-022-06942-1.

Reference Type DERIVED
PMID: 36582001 (View on PubMed)

Other Identifiers

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NL71303.041.19

Identifier Type: -

Identifier Source: org_study_id

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