COLDFIRE-2 study: Colorectal metastatic liver disease: efficacy of irreversible electroporation (IRE) - a phase II clinical trial

Phase 2

Completed

• Conditions: colorectale levermetastasen; Colorectal liver metastases; synonyme; metastasesin the liver derived from colorectal carcinoma; 10019815; 10019818

• Registration Number: NL-OMON44806
• Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

Screening must be performed no longer than 4 weeks prior to study inclusion. Subjects are eligible if they meet the following criteria:
• Histological or cytological documentation of primary colorectal tumor;
• Previous induction chemotherapy due to unresectability; no intra- or extrahepatic disease progression under induction chemotherapy; OR
• Previous chemotherapy for other CRLM, now presenting with renewed CRLM unsuitable for resection or thermal ablation;
• Liver metastases F-18-FDG PET avid and visible on ceCT, size <= 3,5 cm and not eligible for resection or thermal ablation due to location close to a vessel or bile duct;
• Age >= 18 years;
• ASA classification 0 - 3;
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to definite inclusion:
o Hemoglobin >= 5.6 mmol/L;
o Absolute neutrophil count (ANC) >= 1,500/mm3;
o Platelet count >= 100*109/l;
o Total bilirubin <= 1.5 times the upper limit of normal (ULN);
o ALT and AST <= 2.5 x ULN
o Serum creatinine <= 1.5 x ULN or a calculated creatinine clearance * 50 ml/min;
o Prothrombin time or INR < 1.5 x ULN;
o Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician)
• Written informed consent

Exclusion Criteria

Subjects who meet the following criteria at the time of screening will be excluded:
• Lesion > 3,5 cm size;
• History of epilepsy;
• Extrahepatic metastases rendering local therapy unfeasible;
• History of cardiac disease:
o Congestive heart failure >NYHA class 2;
o Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
o Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker/ICD (beta blockers are permitted);
• 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 <= 6 weeks prior to the procedure;
• Chemotherapy <= 6 weeks prior to the procedure;
• Use of anti-convulsives and anti-arrhythmic drugs other than beta blockers for antiepileptic or antiarrhythmic purpose;
• Allergy to contrast media which cannot be adequately prevented with the standard contrast allergy prevention regimen;
• Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is efficacy of IRE as expressed in primary technique<br /><br>effectiveness (by perfoming imaging after 3, 6, 9 and 12 months) also expressed<br /><br>by the local IRE site recurrence (LSR) on a per-lesion basis, and secondary<br /><br>technique effectiveness on a per-lesion basis after repeat procedures for local<br /><br>recurrences whenever indicated. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are (1) safety, derived from number and grade of (serious)<br /><br>adverse events using the common terminology reporting criteria (CTCAE version<br /><br>3.0) as recommended by the CIRSE quality approvement guidelines, (2) technical<br /><br>success, defined as the ability to successfully administer all pulses and to<br /><br>have complete tumor coverage on immediate post-IRE imaging (by IOUS or CT) (3)<br /><br>feasibility of cross-sectional imaging modalities to detect local recurrences<br /><br>after IRE, and (4) symptomatic response using specific quality of life<br /><br>questionnaires.</p><br>