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

NCT04307914 | Active Not Recruiting

• 1 other identifier: NL71303.041.19
• Study Type: interventional
• Target: 216
• Locations: 4 countries
• Sites: 6

Brief Summary

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.

Conditions

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

Keywords

Bone Metastases; Cancer Induced Bone Pain; Pain palliation; Raiotherapy; Radiation oncology; Noninvasive; MR-HIFU; MRgFUS; HIFU; Focused Ultrasound

Outcome Measures

Primary Outcomes (1)

• Pain response - 14 days after completion of treatment

  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 Outcomes (11)

• Pain response - 14 days after inclusion

  14 days

• Patient reported pain scores - patient pain diary

  21 days

• Patient reported pain scores - BPI

  on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months

• 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

Study Arms (3)

External Beam Radiotherapy

ACTIVE COMPARATOR

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

MR-HIFU

EXPERIMENTAL

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

Combination EBRT + MR-HIFU

EXPERIMENTAL

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

Radiation: External beam radiotherapy; Procedure: MR-HIFU

Interventions

External beam radiotherapy 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.

Combination EBRT + MR-HIFU; External Beam Radiotherapy

MR-HIFU 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.

Also known as: MRgFUS, MR guided High Intensity Focused Ultrasound

Combination EBRT + MR-HIFU; MR-HIFU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• UMC Utrecht: lead
• University of Bologna: collaborator
• Turku University Hospital: collaborator
• Universitätsklinikum Köln: collaborator
• University of Roma La Sapienza: collaborator
• Istituto Ortopedico Rizzoli: collaborator
• Isala: collaborator

Study Sites (6)

TUCH Turku

Turku, Finland

Location

University Hospital Cologne

Cologne, Germany

Location

IOR

Bologna, Italy

Location

CSSP

Roma, Italy

Location

University Medical Center Utrecht

Utrecht, Utrecht, 3508GA, Netherlands

Location

Isala Klinieken Zwolle

Zwolle, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 36582001 DERIVED

MeSH Terms

Conditions

Bone Neoplasms; Pain; Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Pathologic Processes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 13, 2020
• Study Start: March 10, 2020
• Primary Completion: September 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-01

Locations

DE (1); NL (2); IT (2); FI (1)