Histotripsy treatment for small liver tumours in Asia

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

This trial will try using histotripsy, a noninvasive focused-ultrasound treatment, to destroy small liver tumors in adults in Asia who are not candidates for surgery or other local therapies.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 21 Years to 99 Years
• Sex: All
• Sponsor: National Cancer Centre, Singapore (other)
• Locations: 3 sites (Singapore and 2 other locations)
• Trial ID: NCT07428356 on ClinicalTrials.gov

What this trial studies

This is a single-arm, multi-centre prospective pilot trial in Singapore using the HistoSonics Edison system to ablate up to three liver lesions per patient (each ≤3 cm) under general anaesthesia. It enrolls adults with primary or secondary liver-limited malignancies or patients with oligoprogressive liver disease while on systemic therapy. Patients will have baseline imaging and labs, undergo histotripsy, and be followed at predefined intervals for clinical, radiologic, and biomarker outcomes. Translational endpoints include immune profiling of PBMCs and cytokines, microbiome analysis, and optional tumor biopsies to characterize biological effects and tolerability in an Asian population.

Who should consider this trial

Good fit: Ideal candidates are adults (≥21 years) with up to three ultrasound-visible liver lesions each ≤3 cm, ECOG 0–1, Child–Pugh A or B7 if cirrhotic, adequate organ function, and who are not eligible for or have declined surgery or other locoregional treatments or have oligoprogressive disease on systemic therapy.

Not a fit: Patients with more than three lesions, lesions larger than 3 cm, lesions not visible/targetable by ultrasound, poor performance status, or diffuse/uncontrolled liver disease are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, histotripsy could offer a noninvasive way to destroy small liver tumors while preserving healthy liver tissue and potentially enhancing anti-tumor immune responses.

How similar studies have performed: Early preclinical and small clinical studies of histotripsy have shown promising feasibility and local tumor control with immune effects, but large-scale evidence is limited and its use specifically in Asian liver cancer populations is novel.

Eligibility criteria

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.

Where this trial is running

Singapore and 2 other locations

• National University Hospital — Singapore, Singapore (NOT_YET_RECRUITING)
• National Cancer Centre Singapore — Singapore, Singapore (RECRUITING)
• Singapore General Hospital — Singapore, Singapore (RECRUITING)

Study contacts

• Principal investigator: Prof Brian Goh, MBBS, MMed, MSc, FRCSEd, FAMS — National Cancer Centre, Singapore
• Study coordinator: Prof Brian Goh, MBBS, MMed, MSc, FRCSEd, FAMS

Conditions: Liver Malignant Tumors, Histotripsy, Ablation of Liver Tumours