Sonoporation and Tumor Microenvironment Response in Colorectal Liver Metastases

NCT07365527 | Recruiting

• 1 other identifier: P-2025-19453
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief 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 can modulate the tumor microenvironment toward a more immune-active state

Conditions

Liver Metastases From Colorectal Cancer

Keywords

liver metastasis; CEUS; Sonoporation; Contrast enhanced ultrasound; colorectal cancer; liver metastases; tumor microenvironment

Outcome Measures

Primary Outcomes (1)

• Immune cell density (CD8+, CD3+) in colorectal liver metastases exposed to LI-CEUS or HI-CEUS, compared to controls.

  ≥7 days after postinterventional

Secondary Outcomes (5)

• Number of participants in the intervention group with treatment-related adverse events assessed by CTCAE v5.0

  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

  Periinterventional

• Differential expression of immune-related genes between CEUS-exposed and control liver metastases

  ≥7 days postinterventional

• Systemic immune response assessed by changes in the circulating cytokine profiles following LI-CEUS and HI-CEUS

  Pre- and ≥7 days postinterventional

• Frequency and type of technical issues encountered during LI-CEUS and HI-CEUS procedures assessed by the operator

  Periinterventional

Study Arms (3)

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

Other: Low-intensity contrast enhanced ultrasound

High-intensity CEUS intervention group

EXPERIMENTAL

12 eligible patients will be randomized to receive HI-CEUS intervention

Other: High-intensity contrast enhanced ultrasound

Interventions

High-intensity contrast enhanced ultrasound OTHER

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.

High-intensity CEUS intervention group

Low-intensity contrast enhanced ultrasound OTHER

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.

Low-intensity CEUS intervention group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Zealand University Hospital: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (2)

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Surgical Department, Zealand University Hospital

Køge, 4600, Denmark

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Christian P Nolsøe, Professor

  Center of Surgical Ultrasound, Surgical department of Zealand University Hospital

  PRINCIPAL INVESTIGATOR

• Ismail Gögenur, Professor

  Center of Surgical Science, Surgical department of Zealand University Hospital

  STUDY DIRECTOR

Central Study Contacts

Maja M Jeppesen, M.D

CONTACT

+45 47323011; mjepp@regionsjaelland.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: January 26, 2026
• Study Start: February 25, 2026
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)