Clinical trial NCT04307914: Focused Ultrasound and RadioTHERapy for Noninvasive Palliative Pain Treatment in Patients With Bone Metastases
Official title: Focused Ultrasound and RadioTHERapy for Noninvasive Palliative Pain Treatment in Patients With Bone Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Turku University Hospital
name: Universitätsklinikum Köln
name: University of Roma La Sapienza
name: Istituto Ortopedico Rizzoli
name: University of Bologna
name: Isala
First posted: 2020-03-13
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pain response - 14 days after completion of treatment
timeFrame: 14 days
Secondary outcomes:
measure: Pain response - 14 days after inclusion
timeFrame: 14 days
measure: Patient reported pain scores - patient pain diary
timeFrame: 21 days
measure: Patient reported pain scores - BPI
timeFrame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
measure: Physician reported toxicity - CTCAE 5.0
timeFrame: at 3 days, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
measure: Patient reported quality of life - EORTC BM22
timeFrame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
measure: Patient reported quality of life - EORTC C15-PAL
timeFrame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
measure: Patient reported quality of life - EQ-5D-5L
timeFrame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
measure: Patient reported quality of life - PGIC
timeFrame: at 1, 2, 4 and 6 weeks, and at 3 and 6 months
measure: Patient reported quality of life - HADS
timeFrame: on baseline, at 1, 2, 4 and 6 weeks, and at 3 and 6 months
measure: Local tumour control
timeFrame: 3 and 6 months
measure: Cost-effectiveness of the treatment
timeFrame: 6 months
Other outcomes:
Locations:
city: Turku
country: Finland
facility: TUCH Turku
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Bologna
country: Italy
facility: IOR
city: Roma
country: Italy
facility: CSSP
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Zwolle
country: Netherlands
facility: Isala Klinieken Zwolle
Study officials:
References: