Pain Relief in Symptomatic Bone Metastases With Adjuvant Hyperthermia MR Guided HIFU (BM-RT-HIFU)

Pain Relief in Patients With Symptomatic Bone Metastases: a Feasibility Pilot Study on Palliative Radiotherapy With Adjuvant Hyperthermia by Magnetic Resonance-guided Focused Ultrasound

Metastatic disease to the bone is a common cause of pain. External beam radiation therapy (EBRT) is the standard palliative treatment BUT pain improvement is observed in 60% to 80%. Combination of hyperthermia (HT) with radiation is strongly compelling. MR is providing accurate, tissue-independent thermometry for intra-procedural guidance of thermal therapy. In this project we aim to combine in an adjuvant setting mild hyperthermia to EBRT for sustained relief of pain in patients with symptomatic bone metastases.

Study Overview

• Status: Recruiting
• Conditions: MRI; Pain; Bone Metastases; Radiotherapy
• Intervention / Treatment: Device: HIFU-MRI guided

Detailed Description

Metastatic disease to the bone is a common cause of pain and other significant symptoms with a detrimental impact into quality of life. Up to 85% of the patients dying from breast, prostate, or lung cancer present bone metastases. External beam radiation therapy (EBRT) is one of the standard palliative treatment modalities effective in palliating painful bone metastases. Using patient-based evaluation method, pain improvement is observed in 60% to 80% of the patients, with 15% to 40% complete pain relief. Combination of hyperthermia (HT) with radiation is strongly compelling as it is based on principles of classic radiobiology, molecular biology, and tumor physiology. Elevating temperature to a supra-physiological level (between 41° and 43°) shows a complementary action when combined with RT with regard to cell killing. Magnetic resonance (MR) imaging is commonly used in clinical routine for radiological diagnostic and staging. Moreover, MR is providing accurate, tissue-independent thermometry for intra-procedural guidance of thermal therapy. In this project we aim to combine in an adjuvant setting mild hyperthermia to EBRT for sustained relief of pain in patients with symptomatic bone metastases. Ex vivo studies for the adaptation of existing MR-guided focused ultrasound (MRgFUS) device were already conducted at University Hospitals of Geneva to the current application demonstrating the high accuracy of the technique for mild hyperthermia treatments. A clinical prospective, interventional, single-center pilot feasibility study will be conducted to assess the clinical application of this technique.

Primary objective

1. Accurate control of spatio-temporal pixel-wise MR thermometry (several hundred pixels): spatial homogeneity of temperature elevation within the tumour and inter-patient reproducibility (expected standard deviation of 0.5°C).
2. Safety and patient tolerance: no adverse effects in surrounding bone and soft tissues, compliance with one-day dual treatment during the first month.

Secondary objectives

1. Complete pain response at 28 days after EBRT + HT based on the International Bone Metastases Consensus Endpoint definition.
2. Pain assessment for the worst pain related to the treated lesion using the Brief Pain Inventory score at baseline, at day 1, day 7, and 28 days after treatment after EBRT + hyperthermia.
3. Health-related quality of life evaluated using self-administered EORTC QLQ-C15-PAL and EORTC QLQ-BM22 (bone metastases module) questionnaires at baseline, day 7, and day 28 after EBRT + hyperthermia.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: sana boudabbous, MD PD; Phone Number: 0041795532444; Email: sana.boudabbous@hcuge.ch

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • Recruiting
    • University Hospitals of Geneva
    • Contact: Sana Boudabbous, Dr; Email: sana.boudabbous@hcuge.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Histologically proven cancer;

  • cancer-related pain corresponding to a site (or sites) of radiologically confirmed bone metastases with a severity score of at least 2 out of 10 according to the Brief Pain Inventory (NRS scale);
  • age ≥ 18 years;
  • indication for a palliative course of EBRT;
  • osteolytic or mixed (osteoblastic/osteolytic) bone metastases ≤ 5 cm in the largest diameter; target tumours accessibility for device (ribs, extremities, pelvis, shoulders or posterior aspects of spinal vertebra) and at least 1 cm from skin and major nerve bundles;

Exclusion Criteria:

• Inability to provide a written informed consent;
• Karnofsky performance status (KPS) < 60; presence of clinical or radiological evidence of spinal cord compression, a pathological fracture, or an impending fracture needing surgical fixation;
• previous EBRT to study site (or sites);
• participation in another clinical trial and any concurrent treatment with any investigational drug within 4 weeks prior to trial entry;
• inability to comply with study and follow up procedures;
• patients having metal implants, pacemakers or clustered markers non-MR compatible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Prospective, interventional, single-center, feasibility pilot study.; 10 patients with radiologically confirmed bone metastases and eligible for a course of palliative EBRT. Eligible patients will be mainly discussed and recruited in a dedicated tumor-board for bone metastases performed in a weekly basis at HUG.	Device: HIFU-MRI guided; HIFU application under MRI guiding to deliver hypothermia to eligible bone metastases before clinical indicated radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accurate elevation of temperature measured by MRI thermometry (degree celsius)	Accurate control of spatio-temporal pixel-wise MR thermometry (several hundred pixels): spatial homogeneity of temperature elevation within the tumour and inter-patient reproducibility (expected standard deviation of 0.5°C).	day 1
Safety and patient tolerance according to The adverse events (CTCAE v5.0) (Art. 2 Abs 58 MDR)	Safety and patient tolerance: no adverse effects in surrounding bone and soft tissues, compliance with one-day dual treatment during the first month. Dermatitis of grade 3 or more - Pain of skin grade 3; Skin atrophy grade 3; Localized edema of grade 3; Bone fracture of grade 3 or more	day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete pain response according to International Bone Metastases Consensus Endpoint score (BPI score)	Complete pain response based on the International Bone Metastases Consensus Endpoint definition.	at 28 days after EBRT + HT
Pain assessment using Brief Pain Inventory score (BPI score)	Pain assessment for the worst pain related to the treated lesion using the Brief Pain Inventory score	at day 1, day 7, and 28 days after treatment after EBRT + hyperthermia.
quality of life using EORTC QLQ-C15-PAL (bone metastases module) questionnaires.	Health-related quality of life evaluated using self-administered EORTC QLQ-C15-PAL (bone metastases module) questionnaires	day 1, day 7, and 28 days after EBRT + hyperthermia.
quality of life using EORTC QLQ-BM22 (bone metastases module) questionnaires.	Health-related quality of life evaluated using self-administered EORTC QLQ-BM22 (bone metastases module) questionnaires	day 7, and day 28 after EBRT + hyperthermia.

Collaborators and Investigators

• Sponsor: Sana Boudabbous

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: BONE METASTASES, PAIN, MRI, HIFU, RADIOTHERAPY
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Wounds and Injuries; Hematologic Diseases; Musculoskeletal Diseases; Neoplastic Processes; Bone Diseases; Body Temperature Changes; Heat Stress Disorders; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases; Hyperthermia
• Other Study ID Numbers: 2020-02998

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No