Effectiveness and Safety of ArcBlate Palliative Treatment for Patients With Painful Bone Metastases: A Pivotal Study

A Pivotal Study to Evaluate the Effectiveness and Safety of ArcBlate Palliative Treatment for Patients With Painful Bone Metastases

A Pivotal Study to Evaluate the Effectiveness and Safety of ArcBlate Palliative Treatment for Patients With Painful Bone Metastases

Study Overview

• Status: Recruiting
• Conditions: Bone Metastases
• Intervention / Treatment: Device: ArcBlate Focused Ultrasound Ablation System; Other: Sham MRgHIFU treatment

Detailed Description

Pain palliation of bone metastasis through localized denervation by thermal ablation.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Feng-Xian Yan; Phone Number: +886-3-5712354; Email: angelay@episonica.com

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 220
    • Not yet recruiting
    • Far Eastern Memorial Hospital
  • Taichung, Taiwan, 407
    • Recruiting
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • Not yet recruiting
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 333
    • Not yet recruiting
    • Chang Gung Memorial Hospital - Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provisional Screening (Screening 1):

  1. Men and women aged 18 and older.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at enrollment.
  3. Patients who are able and willing to give consent and able to attend all study visits.
  4. Patients who are suffering from painful bone metastases.
  5. Patients who refuse other accepted available treatments such as surgery or radiotherapy for pain palliation.
  6. Patient with NRS (0-10 scale) pain score ≥ 4 irrespective of medication.
  7. Able to communicate sensations during the ArcBlate MRgHIFU treatment.
  8. Patients on ongoing systemic anticancer treatment for at least 2 weeks before treatment:
• with same systemic anticancer treatment (as documented from patient medical dossier), And
• worst pain NRS still ≥ 4, And

• do NOT plan to initiate a new chemotherapy for pain palliation throughout the study duration.

  (9) No radiation therapy to targeted (most painful) lesion in the past two weeks before treatment.

  (10) Bisphosphonate intake should remain stable throughout the study duration. (11) Patients will have from 1 to 5 painful lesions and only the most painful lesion will be treated.

  (12) Patients with persistent distinguishable pain associated with 1 site to be treated (if patient has pain from additional sites, the pain from the additional sites must be evaluated as being less intense by at least 2 points on the NRS compared to the site to be treated).

• MRI Screening (Screening 2):

  1. Targeted tumor(s) are ArcBlate MRgHIFU accessible and are located in ribs, extremities (excluding joints), pelvis, shoulders and in the posterior aspects of the following spinal vertebra: Lumbar vertebra (L3 - L5), Sacral vertebra (S1 - S5).
  2. Patient whose targeted (treated) lesion is on bone and the interface between the bone and lesion is deeper than 10-mm from the skin.
  3. Targeted (treated) tumor clearly visible by non-contrast MRI, and ArcBlate MRgHIFU accessible.

• Sonication Screening (Screening 3):

  1. Subjects could tolerate planned test sonications per randomized treatment.

Exclusion Criteria:

• Provisional Screening (Screening 1):

  (1) Patients who either

• need surgical stabilization of the affected bony structure (>7 fracture risk score), Or
• targeted tumor is at an impending fracture site (>7 on fracture risk score), Or

• patients with surgical stabilization of tumor site with metallic hardware. (2) Targeted (treated) lesion is in the skull. (3) Patients on dialysis. (4) Patients with life expectancy < 3-Months. (5) Patients with an acute medical condition (e.g., pneumonia, sepsis) that is expected to hinder them from completing this study.

  (6) Patients with unstable cardiac status including:

• Unstable angina pectoris on medication,
• Patients with documented myocardial infarction within six months of protocol entry,
• Congestive heart failure requiring medication (other than diuretic),

• Patients on anti-arrhythmic drugs. (7) Severe hypertension (diastolic blood pressure > 100 mmHg on medication). (8) Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations (unable to fit into ArcBlate MRgHIFU), etc.

  (9) Patients with an active infection or severe hematological, neurological, or other uncontrolled disease.

  (10) Known intolerance or allergies to the MRI contrast agent (e.g., Gadolinium or Magnevist) and Computed Tomography (CT) contrast agent including advanced kidney disease.

  (11) Severe cerebrovascular disease (multiple CerebroVascular Accident (CVA) or CVA within 6 months).

  (12) Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (approximately 2 hrs.).

  (13) Are participating or have participated in another clinical trial in the last 30 days.

  (14) Patients initiating a new chemotherapy regime, or radiation (for the targeted most painful lesion) within the last 2 weeks before treatment.

  (15) Patients unable to communicate with the investigator and staff. (16) Patients with persistent undistinguishable pain (pain source unidentifiable).

  (17) The targeted tumor is less than 2 points more painful compared to other painful lesions on the site specific NRS.

  (18) Patients with calcified treatment area. (19) Pregnant women.

• MRI Screening (Screening 2):

  1. Target (treated) lesion is less than 10-mm from nerve bundles, bowels or bladder.
  2. Extensive scarring in the energy path of the planned treatment area

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRgHIFU treatment arm; Subjects will be randomized to MRgHIFU treatment arm and will pass the Screening Fail criteria preceded in normal fashion to MRgHIFU treatment at the same session.	Device: ArcBlate Focused Ultrasound Ablation System; MR-guided High Intensity Focused Ultrasound (MRgHIFU)
Sham Comparator: Sham treatment arm; Subjects who will be randomized to sham treatment arm and passed the Screening Fail Criteria (i.e. MRI Screening and Sonication Screening) will undergo a sham MRgHIFU treatment with sonication energy disabled.	Other: Sham MRgHIFU treatment; Sham MRgHIFU treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain response rate to therapy at 30 days after treatment	Pain response rate is assessed by composite endpoint of change from baseline in worst Numerical Rating Scale (NRS) pain score (0-10 scale) and morphine equivalent daily dose (MEDD) intake. Patients with Complete response (CR) or Partial response (PR) are defined as responders to therapy.; Complete response (CR): Pain score 0 without analgesic increase.; Partial response (PR): Pain reduction of 2 or more without analgesic increase; or analgesic reduction of 25% without pain increase. The proportion of responders of the subjects who completed treatment is defined as the pain response rate of this study.	at 30 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in NRS pain score (0-10 scale)	The changes of NRS pain score between post-treatment and pre-treatment. The pain NRS is a single 11-point numeric scale (0-10 scale), with 0 representing one pain extreme (e.g., "no pain") and 10 representing the other pain extreme (e.g., "pain as bad as you can imagine" and "worst pain imaginable").	at 1, 3, 7, 14, 30, 60 and 90 days after treatment
Change from baseline in MEDD intake	The changes of MEDD intake between post-treatment and pre-treatment.	at 7, 14, 30, 60 and 90 days after treatment
Change from baseline in Brief Pain Inventory (BPI-QoL)	The changes of BPI between post-treatment and pre-treatment. The BPI is used to rapidly assess the severity of pain and the impact of pain on daily functions. The BPI has seven interference items, such as general activity, mood, walking ability, normal work (including housework), relations with other people, sleep, and enjoyment of life. The assessment areas of the BPI include severity of pain, impact of pain on daily function, location of pain, pain medications and amount of pain relief in the past 24 hours or the past week.	at 30, 60 and 90 days after treatment
Pain response rate to therapy	Patients with Complete response (CR) or Partial response (PR) are defined as responders to therapy.	at 60 and 90 days after treatment
Quality of Life as measured by EORTC QLQ-C15-PAL questionnaire	The QLQ-C15-PAL contains seven symptom scales (dyspnoea, pain, insomnia, fatigue, appetite loss, nausea and vomiting, and constipation) and three functional scales (physical functioning, emotional functioning, and overall QoL), which were identified as being relevant to the palliative population. Items on the QLQ-C15-PAL questionnaire are rated from 1 (not at all) to 4 (very much), with the exception of the overall QoL status item, which was rated from 1 (very poor) to 7 (excellent). A higher score for the symptom scales represents a higher level of symptomatology and, therefore, a decreased QoL. By contrast, a higher score for the functional scales represents a higher level of functionality and, therefore, an increased QoL. Each scale was transformed to a score ranging from 0 to 100, according to their respective scoring manual.	at 30, 60 and 90 days after treatment
Total number of Adverse Events (AEs)	Total numbers of complications and AEs, including unintended lesions that occur as a result of treatment with MR-HIFU.	within the first 90 days within treatment

Collaborators and Investigators

• Sponsor: EpiSonica

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2023
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: June 27, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Hematologic Diseases; Musculoskeletal Diseases; Neoplastic Processes; Bone Diseases; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases
• Other Study ID Numbers: CTP-BM-22-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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