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

UMC Utrecht

Status

Enrolling

Conditions

Bone Neoplasm

Quality of Life

Cancer Induced Bone Pain

Neoplasm Metastasis

Tumor

Pain

Bone Lesion

Bone Cancer

Bone Metastases

Treatments

Procedure: MR-HIFU

Radiation: External beam radiotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT04307914

NL71303.041.19

Details and patient eligibility

About

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.

Full 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.

Enrollment

216 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

216 participants in 3 patient groups

External Beam Radiotherapy

Active Comparator group

Description:

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.

Treatment:

Radiation: External beam radiotherapy

MR-HIFU

Experimental group

Description:

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.

Treatment:

Procedure: MR-HIFU

Combination EBRT + MR-HIFU

Experimental group

Description:

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

Treatment:

Radiation: External beam radiotherapy

Procedure: MR-HIFU