MR-HIFU Treatment of Painful Osteoid Osteoma

Study Overview
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Brief Summary
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To determine treatment safety and efficacy of MR-HIFU ablation of painful Osteoid Osteoma (OO) in children and young adults.

Detailed Description
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Osteoid Osteoma (OO) is a benign, but painful, bone tumor commonly occurring in children and young adults. Definitive treatment options are CT-guided radiofrequency ablation (RFA) and less commonly, open surgical resection. RFA is less invasive than surgery, but it still requires drilling from the skin through muscle and bone. It also exposes the patient and operator to ionizing radiation. Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU) provides precise and controlled delivery of focused ultrasound energy inside a lesion using an external applicator, without any incisions or drilling. MR-HIFU has been successfully used to treat painful bone metastases in adult clinical trials. Several recent reports, including two publications from our group, show that MR-HIFU is a feasible and safe treatment for OO. MR-HIFU ablation of OO may provide a better alternative to surgical resection or RFA as it is completely non-invasive and does not require ionizing radiation. These two qualities of MR-HIFU are especially beneficial in growing children and young adults. Furthermore, MR-HIFU OO ablation is quick, with expected total procedure time of less than two hours. Such short treatments offer additional safety benefits from reduced anesthesia / sedation requirement compared to surgery and RFA. The investigator's group has performed the first pilot clinical trial in the U.S. to evaluate MR-HIFU treatment for painful osteoid osteoma (PI: K.V. Sharma, NCT02349971). This trial shows that MR-HIFU ablation is feasible, well tolerated, and can be safely performed in a pediatric cohort. Based on these results, the investigators propose a pivotal clinical trial designed to evaluate treatment efficacy as the next logical step required for clinical translation. The investigators hypothesize that noninvasive and radiation-free MR-HIFU ablation for osteoid osteoma will be a clinically effective treatment, with success rate comparable to that currently reported for RFA.

Official Title
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Pivotal / Phase II Clinical Trial of Magnetic Resonance-Guided Focused Ultrasound (MR-HIFU) Treatment of Painful Osteoid Osteoma in Children and Young Adults

Conditions
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Osteoid Osteoma

Intervention / Treatment
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* Device: MR-HIFU treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≤30 years. Diagnosis of OO: All patients diagnosed with painful OO based on characteristic clinical history of pain relieved with NSAID medications AND confirmatory imaging findings characteristic of OO on CT and/or MRI scans. Location of OO: eligible lesions must be located in a bone with acoustic accessibility and within the normal safety margins of MR-HIFU, as specified in the instructions for use. Prior therapy: Patients with prior unsuccessful treatments including CT-RFA and/or surgical resection are eligible for enrollment. Patients < 18 years old must be accompanied by a legal guardian at the time of recruitment. Laboratory: Complete Blood Count (CBC) values within acceptable range for safe administration of anesthesia. Hemoglobin > 9 g/dL. PT, PTT and INR < 1.5 x ULN (including patients on prophylactic anticoagulation) Basic metabolic panel (BMP) and/or Complete metabolic panel (CMP) values within acceptable range for safe administration of anesthesia. Adequate renal function: Age-adjusted normal serum creatinine (see table below) OR a creatinine clearance ≥60 mL/min/1.73 m2 for safe contrast administration Adequate pulmonary function: Defined as no dyspnea at rest, and a pulse oximetry >94% on room air. Exclusion Criteria: Diagnosis of bone lesion other than OO in the judgement of the Principal Investigator. Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which would compromise the patient's ability to tolerate the general anesthetic required for the procedure in the judgment of the Principal Investigator. Implant, prosthesis or scar tissue that would interfere with a safe completion of MR-HIFU. ablation in the judgement of the Principal Investigator. Treatment area nidus <1 cm from a major nerve, spinal canal, bladder, or bowel. Target <1 cm of growth plate (physis). Lesion in the skull. Lesion in the vertebral body. Inability to undergo MRI and/or contraindication for MRI. Inability to tolerate stationary position during MR-HIFU. Patients currently receiving any investigational agents.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br>Patients will undergo MR-HIFU ablation procedure of OO under general anesthesia. Patients will be monitored for disease status and adverse events for 12 months following procedure. Patients with incomplete or partial response at 28 days after MR-HIFU will be permitted a second MR-HIFU procedure. If there is still incomplete pain relief without medication use by 28 days following the second MR-HIFU treatment, patients will be offered standard of care treatment with RFA and followed for one year. | Device: MR-HIFU treatment<br>* MR-HIFU is an innovative technology that allows for non-invasive thermal ablation of tissues and tumors by integrating an external high intensity focused ultrasound (HIFU) transducer with a conventional MRI scanner. The focused ultrasound transducer is placed outside of the body and generates and focuses acoustic energy to heat tumors or other pre-defined focal regions of tissues inside the body. Because the acoustic energy is precisely focused over tiny areas of tissue, potential thermal injury to surrounding tissues is minimal. Cell death inside the selected treatment area occurs via coagulative necrosis while avoiding injury to intervening and adjacent tissues.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v.5 | CTCAE v.5 will be used | 12 months | 
| Pain relief as assessed by pain medication usage | The patient pain and medication diary will be used | 12 months | 
| Pain relief as assessed using the Visual Analog Scale (VAS) | The VAS is a continuous numerical pain scale ranging from 0 (no pain) to 10 (worst possible pain) | 12 months | 
| Pain relief as assessed by using the PROMIS Pain Interference short form | The PROMIS Pain Interference Short Form consists of 8 questions on pain. Each question will be rated from 0 (never), 1 (almost never), 2 (sometimes), 3 (often), and 4 (almost always) | 12 months | 
| Quality of life as assessed by using the Pediatric Quality of Life Inventory (PedsQL) v4.0 | The PedsQL is a 23-item, 4 scale, and 2 domain instrument measuring physical, social, emotional, and cognitive well-being. Each question will be rated from 0 (never) to 4 (almost always) | 12 months | 
| Quality of life as assessed by using the Symptom Distress Scale (SDS) | SDS is a 10-item Likert format instrument that measures symptom intensity and distress. Each question will be rated from 1 (no problems in the area) to 5 (worst problems in this area) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with change in nidus size (mm) as assessed via MRI | Number of participants with change in nidus size (mm) as assessed via MRI | 12 months | 
| Number of participants with change in nidus vascularity as assessed via MRI | Number of participants with change in nidus vascularity as assessed via MRI | 12 months | 
| Number of participants with changes in soft tissue and marrow edema as assessed via MRI | Number of participants with changes in soft tissue and marrow edema as assessed via MRI | 12 months |