Feasibility Evaluation of the Muse Magnetic Resonance Guided Focused Ultrasound System

Study Overview
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Brief Summary
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This is an open-label, single arm, single center, non-randomized feasibility study of the Muse MRgFUS System in subjects with breast cancer. Subjects will undergo partial ablation of half ( 50%) of their tumor followed by surgical resection per standard of care. The partial tumor ablation design will ensure that no information is lost that would impact the subject's standard of clinical care. Because current care often includes testing on the tumor, retaining a portion of viable tumor is advised by the clinical team. To ensure viable tissue confirmation, patients will be enrolled in two cohorts as described in the protocol. We will use imaging correlation, histological evaluation, and subject reported outcomes to assess the safety, tolerability, and efficacy of the Muse MRgFUS System. This proposed study will adhere to the guidelines of subjects receiving a timely tumor resection after diagnosis. All subjects will undergo the definitive procedure of surgical resection per standard of care. Surgical resection cannot be delayed as a result of the ablation and should occur within 6 weeks after the decision to proceed with surgical resection. In cases where a surgery may occur outside of the 6 week window, prior approval from the external DSMC should be obtained.

Official Title
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A Feasibility Evaluation of the Muse Magnetic Resonance Guided Focused Ultrasound System

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: Muse MRgFUS System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects 18 years of age or older with unilateral, unifocal invasive breast cancer undergoing lumpectomy ECOG < 2. ASA (American Society of Anesthesiologists) Physical Status Classification Scale assessment of I-II. Adequate breast size for MUSE device assessed by physician prior to study enrollment. Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Adequate Renal Function defined as an eGFR > 30 mL/min/1.73. Female subjects of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.4.1. Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women < 50 years of age: ---Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and Estradiol and follicle-stimulating hormone levels in the post-menopausal range for the institution; or Underwent surgical sterilization (i.e. bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). Women ≥ 50 years of age: Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or Had radiation-induced menopause with last menses >1 year ago; or Had chemotherapy-induced menopause with last menses >1 year ago; or Underwent surgical sterilization (i.e. bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). Exclusion Criteria: Receiving other investigational agents at the time of study registration. Prior systemic anti-cancer therapy or any investigational therapy for neoadjuvant treatment of breast cancer. Prior radiation therapy to the ipsilateral breast or radiation whose field(s) encompassed the breast within which the current diagnosis of cancer is made. The diagnosis of another malignancy within ≤ 2 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, or bladder or of the cervix). Low risk malignancies may be allowed after discussion with PI and medical monitor. Women with breast implants Pregnant or lactating women Inability to lie prone for 90 minutes as reported by patient or determined by investigator assessment. Known prior adverse reaction or allergy to commonly used sedatives (i.e. versed, propofol) (NCI CTCAE v5.0 Grade ≥ 3). Known prior adverse reaction or allergy to gadolinium contrast (NCI CTCAE v5.0 Grade ≥ 3). Contraindication to MRI as determined by treating phyisican or patient response on MRI patient history and safety questionnaire (Appendix 5) Medical, psychiatric, cognitive, or other conditions in the opinion of the investigator that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. Additional Exclusion Criteria for Cohort 1 patients only Patient's tumor is grade 3 as determined in consulation with pathologist and treating physician. The amount of invasive tumor in the core biopsy specimen is small as determined in consulation with pathologist and treating physician. Core biopsy result is equivocal for HER2 after testing by both in situ hybridization and immunohistochemistry. There is doubt about the handling of the core biopsy specimen (long ischemic time, short time in fixative, different fixative), or the test is suspected by the pathologist to be negative on the basis of testing error.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Interventional Model Description: This is an open-label, single arm, single center, non-randomized feasibility study of the Muse MRgFUS System in subjects with breast cancer.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Muse MRgFUS System<br>Subjects will undergo partial ablation of half ( 50%) of their tumor followed by surgical resection approximately 2-3 weeks after ablation. | Device: Muse MRgFUS System<br>* The intended use of the device is to thermally ablate breast tissue under magnetic resonance image guidance. The thermal ablation is performed non-invasively using extracorporeal focused ultrasound.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency of adverse events (AEs), adverse device effects (ADEs), and serious adverse events (SAEs) characterized by type | evaluate the safety, feasibility, and tolerability of soft tissue ablation with the Muse MRgFUS system as assessed by subject-reported procedural pain and incidence of device- and procedure-related adverse device effects and adverse events | 2 months | 
| frequency of adverse events (AEs), adverse device effects (ADEs), and serious adverse events (SAEs) characterized by severity (as defined by the NCI CTCAE, version 5.0) | evaluate the safety, feasibility, and tolerability of soft tissue ablation with the Muse MRgFUS system as assessed by subject-reported procedural pain and incidence of device- and procedure-related adverse device effects and adverse events | 2 months | 
| frequency of adverse events (AEs), adverse device effects (ADEs), and serious adverse events (SAEs) characterized by seriousness | evaluate the safety, feasibility, and tolerability of soft tissue ablation with the Muse MRgFUS system as assessed by subject-reported procedural pain and incidence of device- and procedure-related adverse device effects and adverse events | 2 months | 
| frequency of adverse events (AEs), adverse device effects (ADEs), and serious adverse events (SAEs) characterized by duration | evaluate the safety, feasibility, and tolerability of soft tissue ablation with the Muse MRgFUS system as assessed by subject-reported procedural pain and incidence of device- and procedure-related adverse device effects and adverse events | 2 months | 
| frequency of adverse events (AEs), adverse device effects (ADEs), and serious adverse events (SAEs) characterized by relationship to the investigational intervention reported during and after the procedure as compared to baseline | evaluate the safety, feasibility, and tolerability of soft tissue ablation with the Muse MRgFUS system as assessed by subject-reported procedural pain and incidence of device- and procedure-related adverse device effects and adverse events | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate ablation efficacy by pathologic assessment | estimate ablation efficacy | 1 month | 
| Disease-free survival (DFS) as defined as the time from the date of ablation to the date of first recurrence or death from any cause | estimate disease-free survival (DFS) at 5 years post ablation | 5 years | 
| Overall survival (OS) as defined as the time from registration until death from any cause | estimate overall survival in this study population at 5 years post ablation | 5 years | 
| Evaluate ablation efficacy by MRI treatment assessment metrics of thermal dose | estimate ablation efficacy | 1 month | 
| Evaluate ablation efficacy by T1-weighted non-perfused volume. | estimate ablation efficacy | 1 month |