The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy

Hepatocellular Carcinoma Clinical Trial

— #HOPE4LIVER US  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04572633
• Other study ID #: CSP1427
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 27, 2021
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: HistoSonics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: July 2026
• Est. primary completion date: January 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatocellular Carcinoma
• Liver Metastases
• Liver Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan Hospital	Ann Arbor	Michigan
United States	University of Chicago	Chicago	Illinois
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University Hospital - UW Health	Madison	Wisconsin
United States	Miami Cancer Institute	Miami	Florida
United States	Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
HistoSonics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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
Secondary	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	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	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