Sonoporation and Tumor Microenvironment Response in Colorect...

About this study

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

Condition: Liver Metastases From Colorectal Cancer
Tested: Low-intensity contrast enhanced ultrasound, High-intensity contrast enhanced ultrasound
Sponsor: Zealand University Hospital

Who can join

Age: 18 years and older
Sex: All sexes
Healthy volunteers: Not accepted

Inclusion 12

Minimum age: 18 years
Study condition: Liver Metastases From Colorectal Cancer
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 17

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

Where

2 sites, 2 recruiting

Rigshospitalet

Copenhagen, Denmark

Recruiting

Surgical Department, Zealand University Hospital

Køge, Denmark