The HistoSonics Edison™ System for Treatment of Primary Solid Renal Tumors Using Histotripsy (#HOPE4KIDNEY)

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the effectiveness and safety of the HistoSonics Edison System for the destruction of kidney tissue by treating primary solid renal tumors.

Detailed Description
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This trial is a prospective, multi-center, single-arm pivotal trial designed to evaluate the effectiveness and safety of the HistoSonics Edison System for the destruction of kidney tissue by treating primary solid renal tumors. Data through 90 days for all enrolled subjects will be summarized in a primary analysis to be submitted for Regulatory Submission to the FDA. Additionally, subjects will be followed for five (5) years post-index procedure, with evaluations at the 14-day, 30-day, 90-day, 180-day and annual time points.

Official Title
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The HistoSonics Edison System for Treatment of Primary Solid Renal Tumors Using Histotripsy (#HOPE4KIDNEY US)

Conditions
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Renal Cancer, Tumor, Solid, Kidney Cancer, Tumor, Tumor, Benign

Intervention / Treatment
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* Device: HistoSonics Edison System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥22 years of age. Subject has signed the Institutional Review Board (IRB) approved trial Informed Consent Form (ICF) prior to any trial related tests/procedures and is willing to comply with trial procedures and required follow-up assessments. Subject is diagnosed with only one (1) non-metastatic solid renal mass ≤3cm confirmed via CT or MRI ≤30 days prior to the index procedure date. Subject has had a biopsy to determine the type of tumor, ≥14 days prior to the index procedure. Subject can tolerate general anesthesia. Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening. Subject meets all the following functional criteria at ≤14 days prior to the planned index procedure date: White Blood Count (WBC) ≥3,000/mm3 Absolute Neutrophil Count (ANC) ≥1,200/mm3 Hemoglobin (Hgb) ≥9 g/dL Platelet count ≥100,000/mm3 White Blood Count (WBC) ≤5 hpf via urinalysis Albumin ≤300 mg/g via urinalysis Subject has an eGFR (Glomerular filtration rate) ≥45mL/min, ≤14 days prior to the planned index procedure date. The tumor selected for histotripsy treatment must be ≤3cm in longest diameter. Subject has an adequate acoustic window to visualize targeted tumor using the HistoSonics Edison System. Exclusion Criteria: Subject is pregnant or planning to become pregnant or nursing (lactating) during the trial period. Subject is being actively treated in another pharmaceutical or device trial ≤30 days prior to planned index procedure date that may interfere with the primary endpoint(s). Subjects who have active cancers (not in remission for the last two years) other than non-melanomatous skin cancers. In the Investigator's opinion, the subject has co-morbid disease(s) or condition(s) that would cause undue risk and preclude safe use of the HistoSonics Edison System. Subject is on dialysis, being considered for dialysis or has acute renal failure. Subject has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or better from any adverse effects (except alopecia and neuropathy) related to previous therapy. Subject has an uncorrectable coagulopathy, International normalized ratio (INR) >1.5 (e.g., known von Willebrand disease, hemophilia, or on anticoagulants), on the planned index procedure date. Subject is taking Aspirin (ASA) or NSAIDS ≤14 days prior to the planned index procedure date. Subject has a life expectancy less than one (< 1) year. In the investigator's opinion, histotripsy is not a treatment option for the subject. Subject has a concurrent condition that could jeopardize the safety of the subject or compliance with the protocol. Subject's targeted tumor has had prior locoregional therapy (e.g., ablation, embolization, radiation). Subject's targeted tumor is not treatable by the HistoSonics Edison System's working ranges (refer to User Guide). In the investigator's opinion, the anticipated risks of intervention outweigh the potential benefits of the intervention. Subject has bilateral kidney tumors. Subject has a genetic predisposition to kidney cancer such as: Von Hippel Lindau (VHL) Hereditary Papillary Renal Carcinoma (HPRC) Birt-Hogg-Dubé Syndrome (BHD) Tuberous Sclerosis Complex (TSC) Hereditary Leiomyomata's Renal Cell Carcinoma (HLRCC) Reed's Syndrome Succinate Dehydrogenase B Deficiency (SDHB) BRCA 1 associated protein -1 (BAP1) Renal Cell Carcinoma MITF predisposed Renal Cell Carcinoma The targeted tumor is an angiomyolipoma. Subject has a known sensitivity to contrast media and cannot be adequately pre-medicated. The targeted tumor is not clearly visible with ultrasound, MRI or CT. Targeted tumor with adequate margin overlaps the renal pelvis, main renal vessel, ureter, or other vital structure. The treatment of the tumor will not allow an adequate margin (as determined by the investigator).

Ages Eligible for Study
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Minimum Age: 22 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
Interventional Model Description: This trial is a prospective, multi-center, single-arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>This is a single arm trial that intends to treat all enrolled subject with the histotripsy device. | Device: HistoSonics Edison System<br>* Non-invasive destruction of kidney tissue using histotripsy, a non-thermal mechanical process of focused ultrasound.<br>* Other names: Histotripsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Effectiveness Endpoint - Primary technique efficacy defined as the percentage of targeted tumors that were successfully eliminated after a single histotripsy session as assessed by contrast enhanced MRI or CT at 90 days. | Primary Effectiveness Endpoint | 90 days Post Index Procedure | 
| Primary Safety Endpoint - Freedom from index procedure related major complications, defined by Clavien-Dindo Classification Grade 3 or higher up to 30 days after the histotripsy procedure. | Primary Safety Endpoint | 30 days Post Index Procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Effectiveness Endpoint- Technical success demonstrating complete coverage of the targeted tumor as determined post-index procedure (≤36 hours) by contrast enhanced MRI or CT in subjects whom treatment was initiated. | Secondary Effectiveness Endpoint - Technical success defined as completion of histotripsy treatment according to protocol and demonstrating complete coverage of the targeted tumor as determined post-index procedure (≤36 hours) by contrast enhanced MRI or CT in subjects whom treatment was initiated. | Up to 36 hours Post Index Procedure | 
| Secondary Safety Endpoint - Freedom from index procedure related major complications, defined by Clavien-Dindo Classification Grade 3 or higher up to 90 days after the histotripsy procedure. | Secondary Safety Endpoint | 90 days Post Index Procedure |