Clinical trial NCT04572633: The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy
Official title: The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER US)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Liver Neoplasms
Hepatocellular Carcinoma
Liver Metastases
Lead sponsor: HistoSonics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-01
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single arm, non-randomized prospective trial.
Primary purpose: TREATMENT

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. 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.

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
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.

Primary outcomes:
measure: Primary Efficacy: Technical Success
timeFrame: ≤36 hours post-index procedure
measure: Primary Safety: Procedure-Related Major Complications
timeFrame: 30 days post-index procedure
Secondary outcomes:
measure: Technical Success
timeFrame: ≤36 hours post-index procedure
measure: Procedure-Related Major Complications
timeFrame: 30 days post-index procedure
measure: Secondary Efficacy: Technique Efficacy
timeFrame: 30 days post-index procedure
measure: Secondary Safety: All Adverse Events
timeFrame: 30 days post-index procedure
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Madison
country: United States
facility: University Hospital - UW Health
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Timothy J Ziemlewicz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Clifford S Cho, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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: 1-year Update of Clinical Outcomes. Ann Surg. 2025 Apr 9. doi: 10.1097/SLA.0000000000006720. Online ahead of print.