COLDFIRE-III Trial: Efficacy of Irreversible Electroporation and Stereotactic Body Radiotherapy for Perivascular and Peribiliary Colorectal Liver Metastases

NCT ID: NCT06185556

Last Updated: 2024-08-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-20
• Study Completion Date: 2031-09-01

Brief Summary

The primary objective of this phase IIb/III, prospective, randomized clinical trial is to compare the efficacy of irreversible electroporation (IRE) with stereotactic body radiotherapy (SBRT) in patients with perivascular or peribiliary colorectal liver metastases (CRLM), that are not amenable for surgical resection or thermal ablation. Efficacy is assessed in terms of local control at 2 years.

Detailed Description

Rationale: Currently, the gold standard for perivascular and peribiliary colorectal liver metastases (CRLM), that are not amenable for surgical resection or thermal ablation, is undetermined. Two non-thermal treatment modalities could provide a solution for these anatomically challenging CRLM: irreversible electroporation (IRE) and stereotactic body radiotherapy (SBRT).

IRE is a new, minimal-invasive image-guided treatment method for tumors not amenable for surgical resection or thermal ablation, due to vicinity near vital structures such as vessels and bile ducts. With IRE, multiple electrical pulses are applied to tumorous tissue. These pulses alter the existing transmembrane potential of the cell membranes, and create 'nanopores', after which the cell dies through loss of homeastasis. SBRT is another non-thermal ablation modality and has important advantages over conventional radiotherapy such as a more precise and greater biological dose delivery and hence less toxicity and presumably better outcome.

Study design: The COLDFIRE-III trial is a phase IIB/III, prospective randomized clinical trial. The primary conducting center will be the Amsterdam UMC (Amsterdam, the Netherlands). The purpose of this study is to assess and compare the efficacy of IRE and SBRT for perivascular or peribiliary CRLM in terms of local control at 2 years. Other objectives are overall survival, additional efficacy endpoints, safety, pain assessments and costs. For the sample size calculations, the log-rank test is used. The (2-year survival) proportion in group 1 (a treatment group) is 0.80. The proportion in group 2 (the alternative treatment group) is 0.55. The significance level of the test is 0.10. A total number of 78 patients will be randomized into one of two arms: arm A (IRE, n = 39) and arm B (SBRT, n = 39).

Study population: 78 patients with 1-3 perivascular and peribiliary lesions of 0-5 cm, ineligible for surgical resection and thermal ablation, suitable for both IRE and SBRT and no or limited extrahepatic disease (1 extrahepatic lesion is allowed, not including positive para-aortic lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis) can be included. Supplementary resections for resectable lesions and thermal ablations for unresectable CRLM are allowed. A maximum number of 10 CRLM are allowed for patients with no extrahepatic disease and a maximum number of 5 lesions are allowed for patients with limited extrahepatic disease. Eligible patients will be stratified according to tumor size (≤3cm vs. 3-5 cm) and (induction) chemotherapy prior to local treatment.

Intervention: Patients will be randomized into one of two arms, arm A (IRE) and arm B (SBRT). The expert panel, consisting of at least two interventional radiologists, two radiation oncologists and two hepatobiliary surgeons, will appoint lesions that are ineligible for surgery of thermal ablation, and suitable for both IRE and SBRT, as target lesions.

Conditions

Colorectal Cancer; Liver Metastases; Liver Metastasis Colon Cancer; Unresectable Solid Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: Irreversible electroporation

Irreversible electroporation (IRE) is a primarily non-thermal, local ablative technique that utilizes electrical pulses to destroy tumor tissue. Theoretically, IRE only affects viable tumor tissue, leaving surrounding vital structures relatively intact. It is therefore considered to cause less morbidity than thermal ablative strategies.

Group Type: ACTIVE_COMPARATOR

Irreversible electroporation

Intervention Type: PROCEDURE

Percutaneous (CT-guided) irreversible electroporation of 1-3 perivascular and peribiliary colorectal liver metastasis.

B: Stereotactic body radiotherapy

Stereotactic body radiotherapy (SBRT) is a form of external beam radiation that has important advantages over conventional radiotherapy such as a more precise and greater biological dose delivery and hence less toxicity and presumably better outcome.

Group Type: ACTIVE_COMPARATOR

Stereotactic body radiotherapy

Intervention Type: RADIATION

Stereotactic body radiotherapy (CT- or MRI-guided) of 1-3 perivascular and peribiliary colorectal liver metastases.

Interventions

Irreversible electroporation

Percutaneous (CT-guided) irreversible electroporation of 1-3 perivascular and peribiliary colorectal liver metastasis.

Intervention Type: PROCEDURE

Stereotactic body radiotherapy

Stereotactic body radiotherapy (CT- or MRI-guided) of 1-3 perivascular and peribiliary colorectal liver metastases.

Intervention Type: RADIATION

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;

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;

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Angiodynamics, Inc.

INDUSTRY

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

M.R. Meijerink

Prof. dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martijn R. Meijerink, Prof.

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Locations

Amsterdam UMC - location VUmc

Amsterdam, North Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Danielle J. Vos, M.D.

Role: CONTACT

interventieradiologie@vumc.nl

+3120-4444571

Facility Contacts

Danielle J. Vos, MD

Role: primary

interventieradiologie@amsterdamumc.nl

20-4444571 ext. +31

Other Identifiers

NL83557.018.23

Identifier Type: -

Identifier Source: org_study_id