The HistoSonics Investigational System for Treatment of Primary Solid Renal Tumors Using Histotripsy

This trial is a prospective, multi-center, single-arm pilot trial designed to evaluate the effectiveness and safety profile of the HistoSonics Investigational System in treating primary solid renal tumors. Following histotripsy treatment of the solid renal tumor, subjects will undergo imaging ≤36 hours post-index procedure to determine technical success. Additionally, subjects will be followed 180 days (6 months) post-index procedure, with evaluations at the 14-day, 30-day, 90-day, and 180-day time points to establish the efficacy and safety profile of the HistoSonics Investigational System.

Inclusion criteria

• Subject is ≥18 years of age.
• Subject has signed the Ethics Committee (EC) 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 a non-metastatic solid renal mass ≤3cm confirmed via CT or MRI ≤ 30 days prior to the index procedure date.
• 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 Cell (WBC) ≥3,000/mm3
• Absolute Neutrophil Count (ANC) ≥1,200/mm3
• Hemoglobin (Hgb) ≥9 g/dL
• Platelet count ≥100,000/mm3 (≥100 10*9/L)
• White Blood Cell (WBC) ≤40 cells/µL via urinalysis
• Albumin ≤300,000 mg/L via urinalysis
• Subject has an eGFR ≥45mL/min, ≤14 days prior to the planned index procedure date.
• International Normalized Ratio (INR) score of <1.5:

• If on anticoagulants, other than aspirin or non-steroidal anti-inflammatory drugs, assessment must be performed on the day of the procedure; OR
• If only on aspirin or non-steroidal anti-inflammatory drugs, assessment must be performed ≤14 days prior to the planned index procedure date; OR
• If not on anticoagulants, assessment must be performed ≤14 days prior to the planned index procedure date
• Biopsy is required to determine the type of tumor and must be performed ≥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 Investigational System.
• Subject will undergo histotripsy treatment of only one (1) tumor during the index procedure, regardless of how many tumors the subject has.

Exclusion criteria

• Subject is pregnant or planning to become pregnant or nursing (lactating) during the trial period.
• Subject is enrolled and being actively treated in another investigational pharmaceutical or device trial ≤30 days prior to planned index procedure date.
• Subject is undergoing active chemotherapy for any cancer ≤14 days prior to planned index procedure date.
• Subject is undergoing active immunotherapy ≤40 days prior to planned index procedure date.
• 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 Investigational System.
• Subject is on dialysis or being considered for dialysis.
• 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 anti-cancer therapy.
• Subject has an uncorrectable coagulopathy other than that induced by aspirin or non-steroidal anti-inflammatory drugs.
• Subject has a planned cancer treatment (e.g., nephrectomy, chemotherapy, immunotherapy etc.) prior to completion of the 30-day follow-up visit.
• Subject has had previous treatments with chemotherapy, radiotherapy, or both that have not been discontinued ≥14 days prior to the planned index procedure date and have not recovered (CTCAE grade 2 or better) from related toxicity (exclusive of alopecia and neuropathy).
• Subject has previous treatment with immunotherapies that has not been discontinued ≥40-days prior to the planned index procedure date and has not recovered from related toxicity (CTCAE grade 2 or better).
• 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.
• Subjects' targeted tumor has had prior locoregional therapy (e.g., ablation, embolization, radiation).
• Subjects' tumor is not treatable by the HistoSonics Investigational System's working ranges (refer to User Guide).
• In the physician's opinion, the anticipated risk of intervention outweighs the potential benefits of the intervention.
• Subject has acute renal failure.
• 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
• 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 diagnostic ultrasound and either magnetic resonance imaging (MRI) or computerized tomography (CT).
• Targeted tumor with adequate margin overlaps the renal pelvis, main renal vessel, ureter, or other vital structure.
• Targeted tumor with adequate margin overlaps a non-targeted tumor visible via imaging.
• The treatment of the tumor will not allow for an adequate margin as determined by the investigator.