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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
This trial is a single arm, non-randomized 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. Data through the 30-day time point will be used for a Regulatory Submission to the Notified Body. Additionally, subjects will be followed for one (1) year post-index procedure, with evaluations at the 6-month and 1-year time points to estimate the efficacy and safety profile of the HistoSonics System as part of post-market clinical follow-up.

Official Title
-----------------
The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER)

Conditions
-----------------
HCC, Liver Tumor, Metastasis

Intervention / Treatment
-----------------
* Device: HistoSonics Histotripsy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 (up to B8) 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 bilirubin <2.5x 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. Exclusion Criteria: Subject is pregnant or planning to become pregnant or nursing (lactating) during the trial period Subject is enrolled in another investigational trial and/or is taking investigational medication or treated with an investigational device ≤30-days prior to index procedure 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 serum creatinine >2.0 mg/dL or estimated glomerular filtration rate (EGFR) <30, unless on dialysis Subject has major surgical procedure or significant traumatic injury ≤2 weeks prior to the index procedure or not fully recovered 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) related to previous anti-cancer therapy Subject has a history of, or suspected to have, bleeding disorders that are uncorrectable Subject has a coagulopathy that is uncorrectable Subject has a planned cancer treatment (e.g. resection, chemotherapy, etc.) from the 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 or has not recovered from related toxicity Subject has previous treatment with immunotherapies that has not been discontinued ≥4 weeks prior to the index-procedure or has not recovered from related toxicity 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 Subject has a concurrent condition that, in the investigator's opinion, could jeopardize the safety of the subject or compliance with the protocol 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 Subjects' targeted tumor(s) has/have had prior locoregional therapy (e.g. ablation, embolization, radiation) Subject is eligible for surgical resection 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This trial is a single arm, non-randomized prospective trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>This is a single arm study that intends to treat all enrolled subject with the histotripsy device. | Device: HistoSonics Histotripsy<br>* The HistoSonics system (System) is intended for the destruction of liver tissue using histotripsy, a non-thermal, mechanical process using focused ultrasound.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success will be determined by evaluating the treatment size and coverage (volume) of the treated tumor via CT or MR imaging. | Technical Efficacy | ≤36 hours post-index procedure | 
| Index procedure related major complications, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicities, up to 30 days post index-procedure. | Safety | 30 days post-index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lack of a nodular or mass-like area of enhancement within or along the edge of the treatment volume | Technique Efficacy | 30 days post-index procedure | 
| All adverse events reported within 30 days of the index procedure. | Safety | 30 days post-index procedure |