Comparing two treatments for colorectal liver metastases

COLDFIRE-III Trial: Perivascular and Peribiliary Colorectal Liver Metastases (0-5cm): Irreversible Electroporation Versus Stereotactic Body Radiotherapy

This study is testing whether a new treatment called irreversible electroporation works better than stereotactic body radiotherapy for people with hard-to-treat colorectal cancer that has spread to the liver.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Amsterdam UMC, location VUmc (Academic / other)
• Drugs / interventions: Chemotherapy, Immunotherapy, radiation
• Locations: 1 site (Amsterdam, North Holland)
• Trial ID: NCT06185556 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of irreversible electroporation (IRE) versus stereotactic body radiotherapy (SBRT) in patients with perivascular or peribiliary colorectal liver metastases that cannot be surgically removed or treated with thermal ablation. The study will assess local control of the tumors over a two-year period, along with overall survival, safety, and cost-effectiveness. Participants will be randomly assigned to receive either IRE or SBRT, both of which are non-thermal treatment options designed to target challenging liver tumors near vital structures.

Who should consider this trial

Good fit: Ideal candidates include patients with 1-3 colorectal liver metastases that are not eligible for surgical resection or thermal ablation due to their proximity to blood vessels or bile ducts.

Not a fit: Patients with extensive extrahepatic disease or those who are not suitable for further systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with difficult-to-treat colorectal liver metastases.

How similar studies have performed: While the use of IRE and SBRT has been explored in other contexts, this specific comparison for colorectal liver metastases is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Histological documentation of primary colorectal tumor is available;
* 1-3 CRLM visible on ceCT and/or MRI, size 0-5 cm and not eligible for resection or thermal ablation due to location close to a vessel or bile duct;
* Additional CRLM are allowed if considered either resectable or ablatable with a maximum of 10 CRLM. In patients with extrahepatic disease, a maximum of 5 additional CRLM is allowed;
* No or limited extrahepatic disease (1 extrahepatic lesion is allowed, with some exclusions mentioned in the exclusion criteria);
* Prior focal liver treatment is allowed;
* Subjects should preferably be treated with neo-adjuvant systemic therapy;
* Subjects with recurrent (either local or distant-hepatic) CRLM after previous focal treatment who are unsuitable for (further) systemic therapy (further downsizing or conversion to resectable disease improbable);
* Adequate bone marrow, liver and renal function as assessed by laboratory requirements to be conducted within 7 days prior to definite inclusion;
* ASA classification 0 - 3;
* Age \>18 years;
* Written informed consent;

Exclusion Criteria:

* Radical treatment unfeasible or unsafe (e.g. insufficient FLR);
* \>10 CRLM; \>5 CRLM when extra-hepatic disease is present;
* Positive para-aortal lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis;
* Subjects who have progressive disease after neo-adjuvant systemic therapy;
* History of epilepsy;
* History of cardiac disease:
* Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
* Compromised liver function (e.g. signs of portal hypertension, INR \> 1,5 without use of anticoagulants, ascites);
* Pregnant or breast-feeding subjects;
* Immunotherapy ≤ 2 weeks prior to the procedure;
* Chemotherapy and/or targeted therapy ≤ 2 weeks prior to the procedure;
* Severe allergy to contrast media not controlled with premedication;
* Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study.

Where this trial is running

Amsterdam, North Holland

• Amsterdam UMC - location VUmc — Amsterdam, North Holland, Netherlands (Recruiting)

Study contacts

• Principal investigator: Martijn R. Meijerink, Prof. — Amsterdam UMC
• Study coordinator: Danielle J. Vos, M.D.

Conditions Colorectal Cancer; Liver Metastases; Liver Metastasis Colon Cancer; Unresectable Solid Tumor; Colorectal liver metastases; colorectal hepatic metastases