The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy

Prior treatment

• Subject is enrolled in another investigational trial and/or is taking investigational medication and/or has been treated with an investigational device ≤30-days prior to planned index procedure date
• Subject has major surgical procedure or significant traumatic injury ≤2 weeks prior to the planned index procedure or not fully recovered (CTCAE grade 1 or better) from side effects/complications of such procedure or trauma
• Subject has not recovered to common terminology criteria for adverse events (CTCAE) grade 1 or better from any adverse effects (except alopecia, fatigue, nausea, vomiting and peripheral neuropathy) related to previous anti-cancer therapy
• Subject has a planned cancer treatment (e.g. resection, chemotherapy, etc.) after the planned index-procedure date and prior to completion of the 30-day follow-up visit
• Subject has previous treatment with bevacizumab that has not been discontinued \>40 days prior to the planned index-procedure date
• Subject has planned bevacizumab treatment prior to completion of the 30-day follow-up visit
• Subject has previous treatments with chemotherapy and/or radiotherapy that has not been discontinued ≥2 weeks prior to the planned index-procedure date and has not recovered (CTCAE grade 1 or better) from related toxicity (except alopecia and peripheral neuropathy)
• Subject has previous treatment with immunotherapies that has not been discontinued ≥4 weeks prior to the index-procedure and has not recovered from related toxicity (CTCAE grade 1 or better)
• Subject has a concurrent condition that, in the investigator's opinion, could jeopardize the safety of the subject or compliance with the protocol
• Subjects' target tumor(s) has/have had prior locoregional therapy (e.g. ablation, embolization, radiation)
• Subject is eligible for surgical resection

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 System
• Subject has a history of, or suspected to have, bleeding disorders that are uncorrectable

Lab values

• Subject has a serum creatinine \>2.0 mg/dL or estimated glomerular filtration rate (EGFR) \<30, unless on dialysis

Other

• Subject is pregnant or planning to become pregnant or nursing (lactating) during the trial period
• Subject has coagulopathy that is uncorrectable
• Subject has a life expectancy less than six (\<6) months
• In the opinion of the Investigator, histotripsy is not a treatment option for the subject
• Subjects' tumor(s) is not treatable by the System's working ranges (refer to User Manual)
• Subject has a known sensitivity to contrast media and cannot be adequately pre-medicated
• Targeted tumor(s) treatment volume overlaps a non-targeted tumor visible via imaging
• The targeted tumor(s) is not clearly visible with diagnostic ultrasound and computed tomography (CT) or magnetic resonance (MR) imaging
• The targeted tumor(s) is located in liver segment 1
• The Planned Treatment Volume intended to cover the targeted tumor includes or encompasses any portion of the main portal vein, common hepatic duct, common bile duct, gallbladder or stomach/bowel.

• Subject is ≥18 years of age
• Subject has signed the Ethics Committee (EC) or 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 hepatocellular carcinoma (HCC) or liver metastases (mets) from other primary cancers
• Subject is able to undergo general anesthesia
• Subject has a Child-Pugh Score of A or B
• Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening
• Subject meets the following functional criteria, ≤7 days prior to the index-procedure:
  • Liver function: Alanine transaminase (ALT) and Aspartate transaminase (AST) \<2.5x upper limit of normal (ULN) and/or bilirubin \<2.5 ULN, and
  • Renal function: serum creatinine \<2x ULN, and
  • Hematologic function: neutrophil count \>1.0 x 10\^9/L and platelet \>50 x 10\^9/L
• Subject has an International Normalized Ratio (INR) score of \<2.0 , ≤7 days prior to the index procedure
• Subject has not responded to and/or has relapsed and/or is intolerant of other available therapies including locoregional therapies, chemotherapy, immunotherapy and targeted therapies
• The tumor(s) selected for histotripsy treatment must be ≤3 cm in longest diameter
• Subject has an adequate acoustic window to visualize targeted tumor(s) using ultrasound imaging
• Subject has a maximum of three (3) tumors to be treated with histotripsy during the index procedure, regardless of how many tumors the subject has.