Liver Neoplasms#HOPE4LIVER USNCT04572633
The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy
A study testing HistoSonics System in people with Liver Neoplasms and Hepatocellular Carcinoma, run by HistoSonics, Inc. at 7 sites in United States.
Trial 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. The co-primary safety and efficacy endpoints must be met for the trial to be successful. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Neoplasms, Hepatocellular Carcinoma, Liver Metastases
- What is being tested?
- HistoSonics System
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 7 sitesUnited States
- Study dates
- 27 Jan 2021to Sep 2027
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening
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- 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
- 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.
Who cannot join
- 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
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- Subject has a history of, or suspected to have, bleeding disorders that are uncorrectable
- Subject has 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 index-procedure 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
- 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' target 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan Hospital
Ann Arbor, Michigan, 48109-5030
University of Chicago
Chicago, Illinois, 60637
University of Kansas Medical Center
Kansas City, Kansas, 66160
University Hospital - UW Health
Madison, Wisconsin, 53792-3252
Miami Cancer Institute
Miami, Florida, 33176
Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, 53226
Tampa General Hospital
Tampa, Florida, 33606
About this study
Official title: 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.
Read the 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.
- Conditions
- Liver Neoplasms, Hepatocellular Carcinoma, Liver Metastases
- Being tested
- HistoSonics System
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HistoSonics SystemDevice
Also called Histotripsy
The HistoSonics System (System) is intended for the destruction of liver tissue using histotripsy, a non-thermal, mechanical process using focused ultrasound.
| Study group | Role | What they receive |
|---|---|---|
| HistoSonics System | Experimental | Not described Receives: Device: HistoSonics System |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: ≤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.
Measured: 30 days post-index procedure
Secondary outcomes (4)
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]
Measured: ≤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]
Measured: 30 days post-index procedure
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]
Measured: 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]
Measured: 30 days post-index procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2020
- Study start27 Jan 2021
- Primary completion9 Jan 2023
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single arm, non-randomized prospective trial.
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- HistoSonics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Timothy J Ziemlewicz, MD, Principal investigator, University of Wisconsin, MadisonClifford S Cho, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04572633
- Sponsor's protocol ID
- CSP1427
- Acronym
- #HOPE4LIVER US
- Status last verified
- Nov 2025
- First submitted
- 28 Sep 2020
- Last updated
- 19 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
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.
PubMed 39225612Ziemlewicz 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.
PubMed 40201962
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER US)
- ClinicalTrials.gov ID
- NCT04572633
- Acronym / sponsor ID
- #HOPE4LIVER US / CSP1427
- Conditions
- Liver Neoplasms, Hepatocellular Carcinoma, Liver Metastases
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 47 participants (actual)
- Lead sponsor
- HistoSonics, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Jan 2021 (actual)
- Primary completion
- 9 Jan 2023 (actual)
- Study completion
- Sep 2027 (estimated)
- First posted
- 1 Oct 2020 (actual)
- Results
- Posted 11 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single arm, non-randomized prospective trial.
| Arm | Type | Receives |
|---|---|---|
| HistoSonics System | Experimental | Device: HistoSonics System |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HistoSonics SystemAlso: HistotripsyThe HistoSonics System (System) is intended for the destruction of liver tissue using histotripsy, a non-thermal, mechanical process using focused ultrasound. | Device | HistoSonics System |
Primary outcome
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 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.
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] 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.
4 secondary outcomes
Technical Success
Time frame: ≤36 hours post-index procedure
Procedure-Related Major Complications
Time frame: 30 days post-index procedure
Secondary Efficacy: Technique Efficacy
Time frame: 30 days post-index procedure
Secondary Safety: All Adverse Events
Time frame: 30 days post-index procedure
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 39225612Mendiratta-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.
- Results publication: PubMed 40201962Ziemlewicz 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy J Ziemlewicz, MD principal investigator
University of Wisconsin, Madison
Clifford S Cho, MD principal investigator
University of Michigan
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HistoSonics System in people with Liver Neoplasms and Hepatocellular Carcinoma, run by HistoSonics, Inc. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Efficacy: Technical Success (time frame: ≤36 hours post-index procedure). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04572633, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025.