Sonoporation and Tumor Microenvironment Response in Colorectal Liver Metastases (CEUSON)

February 24, 2026 updated by: Ismail Gögenur, Zealand University Hospital

Tumor Response to Sonoporation: A Clinical Translational RCT of Contrast-enhanced Ultrasound Induced Changes in Tumor Microenvironment of Colorectal Liver Metastases

This study is an investigator-initiated, randomized controlled trial enrolling patients with colorectal liver metastases. The objectives are to evaluate the safety and efficacy of contrast-enhanced ultrasound (CEUS)-mediated sonoporation as a potential therapeutic intervention and to investigate whether sonoporation can modulate the tumor microenvironment toward a more immune-active state

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The trial is designed as an investigator-initiated, multicenter, prospective, randomized, controlled, two-arm, intervention trial with a matched historical control group aims to evaluate the therapeutic potential of contrast-enhanced ultrasound (CEUS) in patients with colorectal liver metastases (CLM). The primary objectives are to assess whether CEUS can modulate the tumor microenvironment and to determine the safety, tolerability, and feasibility of CEUS as a therapeutic modality. Eligible patients will be randomized to receive either low-intensity CEUS (LI-CEUS) or high-intensity CEUS (HI-CEUS) focused on a designated study metastasis. Safety, feasibility, and success-rate of the intervention will be registered. Minimum seven days post-intervention a biopsy of the study metastasis will be conducted. Subsequent analyses will compare immune cell infiltration, immune-related gene expression, and stromal and vascular remodeling in LI-CEUS- and HI-CEUS-exposed metastases versus historical controls.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Rigshospitalet
        • Contact:
        • Contact:
          • Maja Mønster Jeppesen, MD
          • Phone Number: +45 29939509
          • Email: mjepp@regsj.dk
      • Køge, Denmark, 4600
        • Recruiting
        • Surgical Department, Zealand University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients (≥18 years)
  • Ability to provide written informed consent
  • Histopathological confirmed colorectal adenocarcinoma
  • Scheduled for liver resection or ablation at the Rigshospital, or admitted to oncologic treatment due to colorectal liver metastases (CLM) at Zealand University Hospital
  • Presence of at least one CLM evaluable and accessible by CEUS
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

  • Follow the conditions regarding fertility, pregnancy, or lactation:

    • Women of childbearing potential (WOCBP) are defined as women ranging from the period of menarche till the post-menopausal period, unless permanently sterile (e.g. hysterectomy, bilateral salpingectomy and bilateral oophorectomy), Post-menopause is defined as no menses for 12 months without an alternative medical cause.
    • WOCBP should use a secure and highly effective birth control (as stated in the "Recommendations related to contraception and pregnancy testing in clinical trials", version 1.1, section 4.1, from the Clinical Trials Facilitation and Coordination Group) during the entire period of the trial. In cases of uncertainty regarding pregnancy, pregnancy testing either as highly sensitive serum or urine pregnancy test will be used.

Exclusion Criteria:

  • Oncologic systemic treatment 2 weeks prior to inclusion
  • Prior treatment with an immune checkpoint inhibitor (e.g. anti-PD-L1, anti PD-1, or anti-PD-L2)
  • Inability to reliably distinguish the study metastasis from other hepatic metastases using CEUS
  • Systemic treatment with either corticosteroids (>10 mg daily prednisolone equivalents) or other immunosuppressive medications within 2 weeks prior inclusion. Inhaled or topical steroids and adrenal replacements doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Known history of human immunodeficiency virus (HIV), active or chronic hepatitis B, or C.
  • Pregnancy or lactation.
  • Confirmed dMMR positive primary tumors
  • Inability to comply with study protocol due to psychological, social, or logistical reasons.

  • Contraindications for CEUS:

    • Known hypersensitivity to SonoVue® or any other ultrasound contrast agent
    • Uncontrolled atrial hypertension
    • Known right-to-left intracardiac shunt
    • Severe pulmonary hypertension (SAP >90 mmHg)
    • Adult respiratory distress syndrome.
    • Known hypersensitivity to macrogols
    • Unstable ischemic heart disease or acute coronary syndrome
    • Severe lung disease, e.g. severe chronic obstructive lung disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Historical control group
The historical control group consists of 24 matched patients who underwent liver resection for one or more colorectal liver metastases at Rigshospitalet between 2022 and the end of 2024. These patients serve as a non-intervention comparison cohort.
Experimental: Low-intensity CEUS intervention group
12 eligible patients will be randomized to receive LI-CEUS intervention
Other: Low-intensity contrast enhanced ultrasound
The LI-CEUS arm will receive a 30-minute contrast-enhanced ultrasound session targeting a designated study metastasis. During the procedure, 1 mL of the ultrasound contrast agent SonoVue will be administered every 3 minutes throughout the entire session. Minimum 7 days after the intervention a biopsy of the study metastasis will be conducted.
Experimental: High-intensity CEUS intervention group
12 eligible patients will be randomized to receive HI-CEUS intervention
Other: High-intensity contrast enhanced ultrasound
The HI-CEUS intervention group will recieve a 30-minute CEUS procedure targeting a designated study metastasis. During the procedure, 1 mL of the ultrasound contrast agent SonoVue will be administered every 3 minutes throughout the entire session. A high-intensity ultrasound "flash" will be applied every 30 seconds. This "flash" consists of a brief sequence of ultrasound waves with a high mechanical index that causes complete destruction of microbubbles within the imaging field. Minimum 7 days after the intervention a biopsy of the study metastasis will be conducted.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Immune cell density (CD8+, CD3+) in colorectal liver metastases exposed to LI-CEUS or HI-CEUS, compared to controls.
Time Frame: ≥7 days after postinterventional
≥7 days after postinterventional

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of participants in the intervention group with treatment-related adverse events assessed by CTCAE v5.0
Time Frame: Daily, until 7 days post-interventional
Daily, until 7 days post-interventional
Procedure success of LI-CEUS and HI-CEUS procedures as assessed by operator-defined completion of the planned intervention
Time Frame: Periinterventional
Periinterventional
Differential expression of immune-related genes between CEUS-exposed and control liver metastases
Time Frame: ≥7 days postinterventional
Tissue bulk transcriptional analyses will be evaluated by the Nanostring nCounter platform. Immune-related spatial protein profiling of tumor regions will be evaluated by the GeoMx digital spatial profiler
≥7 days postinterventional
Systemic immune response assessed by changes in the circulating cytokine profiles following LI-CEUS and HI-CEUS
Time Frame: Pre- and ≥7 days postinterventional
Pre- and ≥7 days postinterventional
Frequency and type of technical issues encountered during LI-CEUS and HI-CEUS procedures assessed by the operator
Time Frame: Periinterventional
Periinterventional

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zealand University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Rigshospitalet, Denmark

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christian P Nolsøe, Professor, Center of Surgical Ultrasound, Surgical department of Zealand University Hospital
  • Study Director: Ismail Gögenur, Professor, Center of Surgical Science, Surgical department of Zealand University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 25, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 19, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 26, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 24, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P-2025-19453

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

It is not yet decided.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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