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

Prior treatment

• 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.
• 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 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).

Other illness

• 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 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

Other

• Subject is pregnant or planning to become pregnant or nursing (lactating) during the trial period.
• Subject is on dialysis or being considered for dialysis.
• Subject has a life expectancy less than one (\< 1) year.
• In the investigator's opinion, histotripsy is not a treatment option for the subject.
• 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.
• 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.

• 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.