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

• ClinicalTrials.gov Identifier: NCT04573881
• Recruitment Status: Active, not recruiting
• First Posted: October 5, 2020
• Last Update Posted: January 16, 2024
• Sponsor: HistoSonics, Inc.
• Information provided by (Responsible Party): HistoSonics, Inc.

Tracking Information

• First Submitted Date: September 28, 2020
• First Posted Date: October 5, 2020
• Last Update Posted Date: January 16, 2024
• Actual Study Start Date: June 4, 2021
• Estimated Primary Completion Date: January 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 11, 2024)

• Primary Efficacy: Technical Success [ Time Frame: ≤36 hours post-index procedure ]
  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 Safety: Procedure-Related Major Complications [ Time Frame: 30 days post-index procedure ]
  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]

Original Primary Outcome Measures (submitted: September 28, 2020)

• Technical success as determined, at ≤36 hours post-index procedure, by evaluating the histotripsy treatment size and coverage. [ Time Frame: ≤36 hours post-index procedure ]
  Technical Efficacy
• Descriptive summary of all reported adverse events. [ Time Frame: 30 days post-index procedure ]
  Safety

Current Secondary Outcome Measures (submitted: January 11, 2024)

• Secondary Efficacy: Technique Efficacy [ Time Frame: 30 days post-index procedure ]
  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]
• Secondary Safety: All Adverse Events [ Time Frame: 30 days post-index procedure ]
  Number of adverse events (serious and non-serious) reported within 30 days post-index procedure. [Clinical Events Committee Adjudicated]

Original Secondary Outcome Measures (submitted: September 28, 2020)

Lack of a nodular or mass-like area of enhancement within or along the edge of the treatment volume [ Time Frame: 30 days post-index procedure ]

Technique Efficacy

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK)
• Official Title: The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK)
• 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, 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

This trial is a single arm, non-randomized, multicenter, prospective trial.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Liver Neoplasms
• Hepatocellular Carcinoma
• Liver Metastases

Intervention

Device: HistoSonics System

The HistoSonics System - intended for the destruction of liver tissue using histotripsy, a non-thermal, mechanical process using focused ultrasound.

Other Name: Histotripsy

Study Arms

Experimental: HistoSonics System

Intervention: Device: HistoSonics System

• Publications *: Wah TM, Pech M, Thormann M, Serres X, Littler P, Stenberg B, Lenton J, Smith J, Wiggermann P, Planert M, Vidal-Jove J, Torzilli G, Solbiati L. A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER). Cardiovasc Intervent Radiol. 2023 Feb;46(2):259-267. doi: 10.1007/s00270-022-03309-6. Epub 2022 Nov 15.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 4, 2023): 24
• Original Estimated Enrollment (submitted: September 28, 2020): 45
• Estimated Study Completion Date: July 2026
• Estimated Primary Completion Date: January 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 (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 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
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 or treated with an investigational device ≤30-days prior to index procedure
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 index procedure or not fully recovered 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) 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.) from the 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 or has not recovered from related toxicity
13. 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
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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Italy, Spain, United Kingdom

Administrative Information

• NCT Number: NCT04573881
• Other Study ID Numbers: CSP1473
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: HistoSonics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: HistoSonics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Luigi A Solbiati, MD; Humanitas Hospital

• PRS Account: HistoSonics, Inc.
• Verification Date: January 2024