Liver Metastases From Colorectal CancerCEUSONNCT07365527
Sonoporation and Tumor Microenvironment Response in Colorectal Liver Metastases
A study testing Low-intensity contrast enhanced ultrasound and High-intensity contrast enhanced ultrasound in people with Liver Metastases From Colorectal Cancer, run by Zealand University Hospital at 2 sites in Denmark.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastases From Colorectal Cancer
- What is being tested?
- Low-intensity contrast enhanced ultrasound and High-intensity contrast enhanced ultrasound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 2 sitesDenmark
- Study dates
- 25 Feb 2026to 15 Jan 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark2 sites, 2 recruiting
- Recruiting
Rigshospitalet
Copenhagen, 2100
Hans-Christian Pommergaard, MD, DMSc, PhD, FEBS (HPB), Cli, +45 29 93 95 09, hans-christian.pommergaard@regionh.dk
Maja Mønster Jeppesen, MD, +45 29939509, mjepp@regsj.dk
- Recruiting
Surgical Department, Zealand University Hospital
Køge, 4600
Maja M Jeppesen, MD, +45 47323011, mjepp@regionsjaelland.dk
About this study
Official title: 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
Read the 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.
- Conditions
- Liver Metastases From Colorectal Cancer
- Being tested
- Low-intensity contrast enhanced ultrasound, High-intensity contrast enhanced ultrasound
- Keywords
- liver metastasis, CEUS, Sonoporation, Contrast enhanced ultrasound, colorectal cancer, liver metastases, tumor microenvironment
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-intensity contrast enhanced ultrasoundOther
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.
High-intensity contrast enhanced ultrasoundOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Historical control group | No intervention | 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. |
| Low-intensity CEUS intervention group | Experimental | 12 eligible patients will be randomized to receive LI-CEUS intervention Receives: Other: Low-intensity contrast enhanced ultrasound |
| High-intensity CEUS intervention group | Experimental | 12 eligible patients will be randomized to receive HI-CEUS intervention Receives: Other: High-intensity contrast enhanced ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune cell density (CD8+, CD3+) in colorectal liver metastases exposed to LI-CEUS or HI-CEUS, compared to controls.
Measured: ≥7 days after postinterventional
Secondary outcomes (5)
Number of participants in the intervention group with treatment-related adverse events assessed by CTCAE v5.0
Measured: 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
Measured: Periinterventional
Differential expression of immune-related genes between CEUS-exposed and control liver metastases
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
Measured: ≥7 days postinterventional
Systemic immune response assessed by changes in the circulating cytokine profiles following LI-CEUS and HI-CEUS
Measured: Pre- and ≥7 days postinterventional
Frequency and type of technical issues encountered during LI-CEUS and HI-CEUS procedures assessed by the operator
Measured: Periinterventional
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2026
- Study start25 Feb 2026
- Primary completion15 Jan 2027 (estimated)
- Study completion15 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver Metastases From Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients in the intervention group will be randomized to receive either high-intensity CEUS or low-intensity CEUS. Patients in the intervention group will be compared to a historical control group.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Principal investigator, Ismail Gögenur, Zealand University Hospital
- Investigators
- Christian P Nolsøe, Professor, Principal investigator, Center of Surgical Ultrasound, Surgical department of Zealand University HospitalIsmail Gögenur, Professor, Study director, Center of Surgical Science, Surgical department of Zealand University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07365527
- Sponsor's protocol ID
- P-2025-19453
- Acronym
- CEUSON
- Status last verified
- Feb 2026
- First submitted
- 19 Dec 2025
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: It is not yet decided.
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tumor Response to Sonoporation: A Clinical Translational RCT of Contrast-enhanced Ultrasound Induced Changes in Tumor Microenvironment of Colorectal Liver Metastases
- ClinicalTrials.gov ID
- NCT07365527
- Acronym / sponsor ID
- CEUSON / P-2025-19453
- Conditions
- Liver Metastases From Colorectal Cancer
- Keywords
- liver metastasis, CEUS, Sonoporation, Contrast enhanced ultrasound, colorectal cancer, liver metastases, tumor microenvironment
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- 25 Feb 2026 (actual)
- Primary completion
- 15 Jan 2027 (estimated)
- Study completion
- 15 Jan 2027 (estimated)
- First posted
- 26 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- Model description
- Patients in the intervention group will be randomized to receive either high-intensity CEUS or low-intensity CEUS. Patients in the intervention group will be compared to a historical control group.
| Arm | Type | Receives |
|---|---|---|
| Historical control group | No intervention | –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. |
| Low-intensity CEUS intervention group | Experimental | Other: Low-intensity contrast enhanced ultrasound12 eligible patients will be randomized to receive LI-CEUS intervention |
| High-intensity CEUS intervention group | Experimental | Other: High-intensity contrast enhanced ultrasound12 eligible patients will be randomized to receive HI-CEUS intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-intensity contrast enhanced ultrasoundThe 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. | Other | Low-intensity CEUS intervention group |
| High-intensity contrast enhanced ultrasoundThe 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. | Other | High-intensity CEUS intervention group |
Primary outcome
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
5 secondary outcomes
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
Procedure success of LI-CEUS and HI-CEUS procedures as assessed by operator-defined completion of the planned intervention
Time frame: Periinterventional
Differential expression of immune-related genes between CEUS-exposed and control liver metastases
Time frame: ≥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
Frequency and type of technical issues encountered during LI-CEUS and HI-CEUS procedures assessed by the operator
Time frame: Periinterventional
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Individual participant dataSharing planned: No. It is not yet decided.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christian P Nolsøe, Professor principal investigator
Center of Surgical Ultrasound, Surgical department of Zealand University Hospital
Ismail Gögenur, Professor study director
Center of Surgical Science, Surgical department of Zealand University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low-intensity contrast enhanced ultrasound and High-intensity contrast enhanced ultrasound in people with Liver Metastases From Colorectal Cancer, run by Zealand University Hospital at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maja M Jeppesen, M.D (+45 47323011, mjepp@regionsjaelland.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.