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

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

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. The co-primary safety and efficacy endpoints must be met for the trial to be successful.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Neoplasms; Hepatocellular Carcinoma; Liver Metastases
• Intervention / Treatment: Device: HistoSonics System

Detailed Description

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.

The #HOPE4LIVER US trial required pooling data from #HOPE4LIVER US and #HOPE4LIVER EU/UK (NCT04573881). Subjects were treated with the same intervention (HistoSonics System) using identical protocols tailored to the regulatory requirements for each geography.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5030
      • University of Michigan Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-3252
      • University Hospital - UW Health
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin/Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
4. Subject is able to undergo general anesthesia
5. Subject has a Child-Pugh Score of A or B
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 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
8. Subject has an International Normalized Ratio (INR) score of <2.0 , ≤7 days prior to the index procedure
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.

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 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 index-procedure 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' target 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HistoSonics System	Device: HistoSonics System; The HistoSonics System (System) is intended for the destruction of liver tissue using histotripsy, a non-thermal, mechanical process using focused ultrasound.; Other Names: Histotripsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy: Technical Success	Technical success, defined as the treatment volume/treatment dimensions being greater than or equal to the targeted tumor, and with complete tumor coverage, via computed tomography (CT) or magnetic resonance (MR) imaging. [Core Laboratory Adjudicated] Primary efficacy was assessed per tumor with a performance goal of greater than 70%. Primary efficacy was assessed after the first forty (40) consecutive evaluable subjects were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success.	≤36 hours post-index procedure
Primary Safety: Procedure-Related Major Complications	Number of index procedure related major complications, including device-related events defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicities observed up to 30-days post index-procedure. [Clinical Events Committee Adjudicated] Primary safety was assessed per participant with a performance goal of less than 25%. Primary safety was assessed on all subjects enrolled, after the first forty (40) consecutive subjects evaluable for technical success were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success. Enrollment of 44 total subjects was required to assess forty (40) subjects evaluable for technical success.	30 days post-index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy: Technique Efficacy	Technique efficacy, defined as the lack of a nodular or mass-like area of enhancement within or along the edge of the treatment volume assessed via CT or MR imaging at 30-days post-procedure. [Core Laboratory Adjudicated]	30 days post-index procedure
Secondary Safety: All Adverse Events	Number of adverse events (serious and non-serious) reported within 30 days post-index procedure. [Clinical Events Committee Adjudicated]	30 days post-index procedure
Technical Success	Technical success, defined as the treatment volume/treatment dimensions being greater than or equal to the targeted tumor, and with complete tumor coverage, via computed tomography (CT) or magnetic resonance (MR) imaging. [Core Laboratory Adjudicated]	≤36 hours post-index procedure
Procedure-Related Major Complications	Number of index procedure related major complications, including device-related events defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicities observed up to 30-days post index-procedure. [Clinical Events Committee Adjudicated]	30 days post-index procedure

Collaborators and Investigators

• Sponsor: HistoSonics, Inc.
• Investigators: Principal Investigator: Timothy J Ziemlewicz, MD, University of Wisconsin, Madison; Principal Investigator: Clifford S Cho, MD, University of Michigan

Publications and helpful links

General Publications

• Mendiratta-Lala M, Wiggermann P, Pech M, Serres-Creixams X, White SB, Davis C, Ahmed O, Parikh ND, Planert M, Thormann M, Xu Z, Collins Z, Narayanan G, Torzilli G, Cho C, Littler P, Wah TM, Solbiati L, Ziemlewicz TJ. The #HOPE4LIVER Single-Arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors. Radiology. 2024 Sep;312(3):e233051. doi: 10.1148/radiol.233051.
• Ziemlewicz TJ, Critchfield JJ, Mendiratta-Lala M, Wiggermann P, Pech M, Serres-Creixams X, Lubner M, Wah TM, Littler P, Davis CR, Narayanan G, White SB, Ahmed O, Collins ZS, Parikh ND, Planert M, Thormann M, Torzilli G, Solbiati LA, Cho CS. The #HOPE4LIVER single-arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors: 1-year Update of Clinical Outcomes. Ann Surg. 2025 Apr 9. doi: 10.1097/SLA.0000000000006720. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Actual): January 9, 2023
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Estimated): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy; immunotherapy; HCC; radiotherapy; metastatic; liver; Liver Cancer; ablation; metastasis; resection; tumor; nodule; histotripsy; hepatocellular Carcinoma; Liver cell carcinoma; nodular; cancer treatment; locoregional therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: CSP1427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes