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.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Liver Neoplasms; Hepatocellular Carcinoma; Liver Metastases	Device: HistoSonics System	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• 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
• Official Title: The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER EU/UK)
• Actual Study Start Date: June 4, 2021
• Estimated Primary Completion Date: January 2026
• Estimated Study Completion Date: July 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: HistoSonics System	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

Outcome Measures

Primary Outcome Measures :

1. 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]
2. 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]

Secondary Outcome Measures :

1. 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]
2. 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]

Eligibility Criteria

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

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

Contacts and Locations

Locations

Germany

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, Germany

Universitätsklinikum Magdeburg Klinik für Radiologie und Nuklearmedizin

Magdeburg, Germany, 39120

Italy

Istituto Clinico Humanitas - Humanitas Mirasole S.P.A.

Milano, Italy

Spain

Vall d'Hebron

Barcelona, Spain

United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom, LS9 7TF

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom, NE7 7DN

Sponsors and Collaborators

HistoSonics, Inc.

Investigators

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

More Information

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.

• Responsible Party: HistoSonics, Inc.
• ClinicalTrials.gov Identifier: NCT04573881
• Other Study ID Numbers: CSP1473
• First Posted: October 5, 2020
• Last Update Posted: January 16, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Liver Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases