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

NCT04573881 | Active Not Recruiting Results DMC FDA Device

• 1 other identifier: CSP1473
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 6

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.

Conditions

Liver Neoplasms; Hepatocellular Carcinoma; Liver Metastases

Outcome Measures

Primary Outcomes (2)

• 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. \[Core Laboratory Adjudicated\]

  ≤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. \[Clinical Events Committee Adjudicated\]

  30 days post-index procedure

Secondary Outcomes (2)

• Secondary Efficacy: Technique Efficacy

  30 days post-index procedure

• Secondary Safety: All Adverse Events

  30 days post-index procedure

Study Arms (1)

HistoSonics System

EXPERIMENTAL

Device: HistoSonics System

Interventions

HistoSonics System DEVICE

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

Also known as: Histotripsy

HistoSonics System

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 and/or has been treated with an investigational device ≤30-days prior to planned index procedure date
• 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 planned index procedure or not fully recovered (CTCAE grade 1 or better) 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, fatigue, nausea, vomiting and peripheral neuropathy) 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.) after the planned 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 and has not recovered (CTCAE grade 1 or better) from related toxicity (except alopecia and peripheral neuropathy)
• 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)
• 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

Sponsors & Collaborators

• HistoSonics, Inc.: lead

Study Sites (6)

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, Germany

Location

Universitätsklinikum Magdeburg Klinik für Radiologie und Nuklearmedizin

Magdeburg, 39120, Germany

Location

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

Milan, Italy

Location

Vall d'Hebron

Barcelona, Spain

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, NE7 7DN, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 36380155 BACKGROUND

• 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.

  PMID: 39225612 RESULT

• 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: One-year Update of Clinical Outcomes. Ann Surg. 2025 Dec 1;282(6):908-916. doi: 10.1097/SLA.0000000000006720. Epub 2025 Apr 9.

  PMID: 40201962 RESULT

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Limitations and Caveats

Due to completion of the primary analysis in #HOPE4LIVER US (NCT04572633) that included powered efficacy and safety hypothesis testing on combined US and EU/UK participants, #HOPE4LIVER EU/UK trial enrollment was stopped early. Therefore, there is an insufficient number of target participants needed to achieve target power and statistically reliable results for the primary endpoints for #HOPE4LIVER EU/UK.

Results Point of Contact

• Title: Vice President of Clinical Affairs
• Organization: HistoSonics, Inc.

clinicaltrials@histosonics.com

(877) 740-0543

Study Officials

• Luigi A Solbiati, MD

  Humanitas Research Hospital IRCCS, Rozzano-Milan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 5, 2020
• Study Start: June 4, 2021
• Primary Completion: September 29, 2022
• Study Completion (Estimated): August 1, 2027
• Last Updated: January 12, 2026
• Results First Posted: August 19, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); GB (2); DE (2); ES (1)