Histotripsy for Ablation of Liver Tumours in Asia (HALT)

Histotripsy Ablation for Liver Tumours (HALT): A Multi-centre Prospective Pilot Study on the Safety and Efficacy of Histotripsy in Asian Primary and Secondary Liver Malignancies

The HALT study aims to evaluate histotripsy in an Asian population for both primary (HCC, CCA) and secondary liver malignancies with liver-limited or oligoprogressive disease. In addition to safety and local control, the study incorporates translational endpoints including immune profiling (PBMCs, cytokines), microbiome shifts, and optional tumour biopsies. This trial will provide critical data on the feasibility, tolerability, and biological impact of histotripsy in a region with the highest burden of liver cancer.

Study Overview

• Status: Recruiting
• Conditions: Liver Malignant Tumors
• Intervention / Treatment: Device: Histotripsy using HistoSonics Edison™ System

Detailed Description

This will be a single-arm, multi-centre, prospective pilot study enrolling patients with:

A) Liver limited malignancies (primary or secondary) not eligible for/declined resection or other locoregional treatment modalities.

B) All solid cancer patients (e.g., HCC, colorectal, breast, pancreatic cancers etc) undergoing systemic therapy with oligoprogressive liver disease (defined as ≤ 3 liver limited progressive lesions, ≤ 3 cm in maximum diameter having received > 3 months of systemic therapy).

Patients will undergo baseline imaging and laboratory investigations, followed by histotripsy treatment under general anaesthesia. Post-procedure assessments will be performed at predefined intervals for clinical, radiologic, and biomarker evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof Brian Goh, MBBS, MMed, MSc, FRCSEd, FAMS; Phone Number: +65 63265440; Email: brian.goh@singhealth.com.sg
• Study Contact Backup: Name: Sandra Hsing; Email: sandra.hsing.san@nccs.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
    • Contact: A/Prof Chow Wei TOO, MBBS, FRCR, MMed, FAMS; Email: too.chow.wei@singhealth.com.sg
  • Singapore, Singapore, 119074
    • Not yet recruiting
    • National University Hospital
    • Contact: Dr Shao-Jin ONG, MBBS, FRCR (UK), FAMS; Email: shao_jin_ong@nuhs.edu.sg
  • Singapore, Singapore, 168583
    • Recruiting
    • National Cancer Centre Singapore
    • Contact: Prof Brian Goh, MBBS, MMed, MSc, FRCSEd, FAMS; Phone Number: +65 63265440; Email: brian.goh@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥21 years at the time of consent.

2. Histologically/cytologically confirmed cancers (imaging diagnosis as per AASLD allowed for HCC):

   A) Liver limited malignancies (primary or secondary) not eligible for/declined resection or other locoregional treatment modalities.

   B) All solid cancer patients (e.g., HCC, colorectal, breast, pancreatic cancers etc) undergoing systemic therapy with oligoprogressive liver disease (defined as ≤ 3 liver limited progressive lesions, ≤ 3 cm in maximum diameter having received > 3 months of systemic therapy).

3. Characteristics of hepatic lesions intended for treatment:

   • Up to 3 hepatic lesions.
   • Tumour ≤ 3 cm in longest diameter.
   • Lesion(s) must be visible and targetable by ultrasound.
4. ECOG Performance Status 0-1.
5. Child-Pugh class A or B7 liver function for patients with underlying cirrhosis.

6. Adequate hematologic and organ function within 14 days prior to treatment:

   • Haemoglobin ≥ 9.0 g/dL
   • Platelets ≥ 75,000/mm³
   • INR ≤ 1.5 × ULN
   • Estimated (by Cockroft-Gault or Modification of Diet in Renal Disease (MDRD) or measured creatinine clearance ≥ 50ml/min.
   • Total bilirubin ≤ 1.5 × upper limit normal or direct bilirubin ≤ ULN for participants with total bilirubin > 1.5 × ULN (participants with known history of elevated indirect bilirubin level suggestive of extrahepatic source of elevation e.g. Gilbert's disease may be recruited with bilirubin levels ≤ 3 × ULN)
   • AST and ALT ≤ 5 × ULN
7. Ability to undergo general anaesthesia, as confirmed by pre-anaesthetic assessment.
8. Life expectancy ≥ 3 months in the opinion of the investigator.
9. Willing and able to comply with study visits and procedures.
10. Written informed consent obtained prior to any study-related procedures.

Exclusion Criteria:

1. Extrahepatic disease progression requiring immediate systemic intervention, including new brain metastases or malignant ascites.
2. Vascular invasion, defined as gross involvement or encasement of major portal vein or hepatic vein branches.
3. Tumours located adjacent (<5 mm) to hollow viscera (e.g., stomach, colon) where histotripsy poses perforation risk.
4. Lesions poorly visualized on ultrasound or not targetable due to overlying ribs or gas.

5. Severe or uncontrolled comorbidities including:

   • Uncontrolled hypertension or cardiovascular disease
   • Active infection (requiring systemic therapy)
   • Severe chronic obstructive pulmonary disease or hypoxia
6. Contraindications to general anaesthesia or surgery.
7. Pregnancy or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days prior to treatment.
8. Participation in another interventional trial within 4 weeks prior to enrollment, or concurrent participation in a therapeutic study.
9. Any condition that, in the investigator's judgment, may compromise the patient's safety or interfere with protocol adherence.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Histotripsy Group; Histotripsy for Ablation of Liver Tumours.	Device: Histotripsy using HistoSonics Edison™ System; The histotripsy procedure will be performed using the HistoSonics Edison™ System, an image-guided, non-invasive focused ultrasound platform specifically designed for mechanical tissue fractionation. Key steps include general anaesthesia and positioning, pre-treatment planning and imaging, and histotripsy ablation procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month local control rate.	Proportion of patients with absence of local tumour progression at the treated site as per RECIST version 1.1 criteria.	6 months post-procedure.
Major complication rate.	Incidence of treatment-related adverse events (AEs) of grade ≥3 (CTCAE v5.0) within 30 days post-procedure.	30 days post-procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
36-hour technical success rate.	Proportion of patients with tumour treated volume ≥ targeted volume with complete tumour coverage, evaluated using contrast-enhanced MRI/CT.	36 hours post-procedure.
30-day technique efficacy rate.	Proportion of patients with absence of nodular or mass-like enhancement within or along the treatment volume	30 days post-procedure.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Response Evaluation and patterns of progression.	Percentage change of tumour sizes from baseline to each of the timepoints specified in the protocol. Pattern of progression will be tabulation (frequency + percentages) of the pattern of progression	3 months, 6 months, 1 year and 2 years post-procedure.
Changes in quality-of-life post-histotripsy, based on EORTC QLQ-C30 scores.	Change of scores based on EORTC QLQ-C30 for liver malignancies from baseline to each of the timepoints specified in the protocol	30 days, 3 months, 6 months, 1 year and 2 years post-procedure.
Changes in quality-of-life post-histotripsy, based on EORTC QLQ-HCC18 scores.	Change of scores based on EORTC QLQ-HCC18 for liver malignancies from baseline to each of the timepoints specified in the protocol	30 days, 3 months, 6 months, 1 year and 2 years post-procedure.
Immune Response Analysis based on Information from Immune Biomarkers.	Evaluation of changes in circulating immune biomarkers post-histotripsy.	36 hours, 14 days, 30 days, 3 months and 6 months post-procedure.
Immune Response Analysis based on Information from Microbiome.	Evaluation of changes in circulating microbiome post-histotripsy.	36 hours, 14 days, 30 days, 3 months and 6 months post-procedure.

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore
• Investigators: Principal Investigator: Prof Brian Goh, MBBS, MMed, MSc, FRCSEd, FAMS, National Cancer Centre, Singapore

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2025
• Primary Completion (Estimated): November 7, 2027
• Study Completion (Estimated): May 7, 2029

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Histotripsy; Ablation of Liver Tumours
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 2025-0635

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes