The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK)

The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK)

This trial is a single arm, non-randomized prospective trial. The objective of this trial is to evaluate the efficacy and safety of the HistoSonics System for the treatment of primary or metastatic tumors located in the liver.

This trial is a single arm, non-randomized, multicenter, prospective trial. Following histotripsy treatment of liver tumor(s), subjects will undergo imaging ≤36 hours post-index procedure to determine technical success. Subjects will then be followed for 30 days. Additionally, subjects will be evaluated at 6 months and followed annually for up to five (5) years post-index procedure.

Inclusion Criteria:

1. Subject is ≥18 years of age

2. 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

3. Subject is diagnosed with hepatocellular carcinoma (HCC) or liver metastases (mets) from other primary cancers

   • Subject that is an HCC patient must have a targetable lesion(s) which meets the United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS-OPTN) class 5 diagnostic criteria for HCC
   • Subject that is diagnosed with liver metastases must have prior diagnosis of primary tumor or metastatic tumor to identify the primary cancer type. Subjects must have untreated new or growing liver tumor(s) radiologically consistent with metastases. Note: A biopsy is required to confirm metastatic disease and the pathological results must be obtained prior to the index procedure (does not need to be a targeted tumor(s))

4. Subject is able to undergo general anesthesia

5. Subject has a Child-Pugh Score of A or B (up to B8)

6. Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening

7. Subject meets the following functional criteria, ≤7 days prior to the planned index-procedure date:

   • Liver function: Alanine transaminase (ALT) <2.5x upper limit of normal (ULN) and Aspartate transaminase (AST) <2.5x ULN and 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

8. Subject has an International Normalized Ratio (INR) score of <2.0 , ≤7 days prior to the planned index procedure date

9. 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.

10. The tumor(s) selected for histotripsy treatment must be ≤3 cm in longest diameter

11. Subject has an adequate acoustic window to visualize targeted tumor(s) using ultrasound imaging

12. 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.

Note: If the subject is treated with surgical resection prior to the index procedure, the resection must be performed ≥2 weeks prior to the planned index-procedure date

Exclusion Criteria:

1. Subject is pregnant or planning to become pregnant or nursing (lactating) during the trial period
2. 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
3. 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
4. Subject has a serum creatinine >2.0 mg/dL or estimated glomerular filtration rate (EGFR) <30, unless on dialysis
5. 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
6. 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
7. Subject has a history of, or suspected to have, bleeding disorders that are uncorrectable
8. Subject has a coagulopathy that is uncorrectable
9. 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
10. Subject has previous treatment with bevacizumab that has not been discontinued >40 days prior to the planned index-procedure date
11. Subject has planned bevacizumab treatment prior to completion of the 30-day follow-up visit
12. 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)
13. Subject has previous treatment with immunotherapies that has not been discontinued ≥4 weeks prior to the planned index-procedure date and has not recovered from related toxicity (CTCAE grade 1 or better)
14. Subject has a life expectancy less than six (<6) months
15. In the opinion of the Investigator, histotripsy is not a treatment option for the subject
16. Subject has a concurrent condition that, in the investigator's opinion, could jeopardize the safety of the subject or compliance with the protocol
17. Subjects' tumor(s) is not treatable by the System's working ranges (refer to User Manual)
18. Subject has a known sensitivity to contrast media and cannot be adequately pre-medicated
19. Subjects' targeted tumor(s) has/have had prior locoregional therapy (e.g. ablation, embolization, radiation)
20. Subject is eligible for surgical resection
21. Targeted tumor(s) treatment volume overlaps a non-targeted tumor visible via imaging
22. The targeted tumor(s) is not clearly visible with diagnostic ultrasound and computed tomography (CT) or magnetic resonance (MR) imaging
23. The targeted tumor(s) is located in liver segment 1
24. 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