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Sonoporation and Tumor Microenvironment Response in Colorectal Liver Metastases

ConditionLiver Metastases From Colorectal Cancer
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorZealand University Hospital

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Low-intensity contrast enhanced ultrasound

    Other intervention

    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 ultrasound

    Other intervention

    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.

Treatment groups

48 Participants
are divided into 3 treatment groups
Group A: Historical control groupNo intervention 0 interventions
Group B: Low-intensity CEUS intervention groupExperimental treatment 1 intervention
Group C: High-intensity CEUS intervention groupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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

Secondary outcomes

1

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
2

Procedure success of LI-CEUS and HI-CEUS procedures as assessed by operator-defined completion of the planned intervention

Time frame
Periinterventional
3

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

Time frame
≥7 days postinterventional
4

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

Time frame
Pre- and ≥7 days postinterventional

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Zealand University Hospital

Lead sponsor

Rigshospitalet, Denmark

Collaborator

Source ClinicalTrials.gov
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