Efficacy of Irreversible Electroporation (IRE) for Central Colorectal Liver Metastases

NCT02082782 | Completed Phase 2 DMC

• 1 other identifier: COLDFIRE-2 study
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

Brief Summary

Irreversible electroporation (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. The purpose of this study is to investigate the efficacy of percutaneous and open IRE in the treatment of patients with colorectal liver metastases (CRLM) that are unsuitable for resection or thermal ablation due to vicinity to vulnerable structures such as vessels and bile ducts. Other objectives are safety, feasibility (technical success) and imaging characteristics on follow-up (PET-)CT and PET-MRI and the value of these imaging modalities in dianosing local site recurrence (LSR) or residual disease (RD). 29 patients with histologically confirmed colorectal carcinoma who present with unresectable and not thermally ablative CRLM\< 3.5cm suitable for IRE will undergo percutaneous or open irreversible electroporation of the tumor using CT and ultrasound guidance. All (serious) adverse events are registered. One day post-IRE MRI is performed to assess technical success. Follow-up will consist of frequent (PET-)CT and (PET-)MRI scanning to localize residual or recurrent disease. Overall technique effectiveness is determined 1 year after treatment. The investigators hypothesize that IRE for central CRLM will lead to good tumor control without causing severe complications.

Conditions

Colorectal Liver Metastases

Keywords

Colorectal liver metastases (CRLM); Tumor ablation; Irreversible electroporation (IRE); Interventional oncology; NanoKnife; Colorectal liver metastasis, unresectable and not-thermally ablative due to location near vulnerable structures like vessels or bile ducts

Outcome Measures

Primary Outcomes (1)

• Efficacy

  The primary objective of this project is to evaluate the efficacy (percentage of lesions that show no sign of recurrence 12 months after the initail IRE procedure) of IRE for CRLM on cross-sectional imaging performed after respectively 6 weeks, and after 3, 6, 9 and 12 months. Research has shown that 95% of all recurrences after RFA of CRLM are diagnosed within one year after treatment. Therefore, one year follow-up will allow for accurate calculation of efficacy. Exact secondary efficacy rate may require follow-up longer than 12 months since this includes lesions that have been re-treated due to local site recurrence/local tumor residue (which will be individualized for each patient after re-treatment of LSR/LTR).

  12 months

Study Arms (1)

irreversible electroporation (IRE)

EXPERIMENTAL

Single arm study: percutaneous or open irreversible electropration of CRLM

Procedure: Irreversible electroporation (IRE)

Interventions

Irreversible electroporation (IRE) PROCEDURE

Percutaneous (CT-guided) or open (US-guided) irreversible electroporation of central colorectal liver metastasis.

Also known as: NanoKnife

irreversible electroporation (IRE)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 more than 18 years;
• ASA classification 0 - 3;
• Hemoglobin ≥ 5.6 mmol/L;
• Absolute neutrophil count (ANC) ≥ 1,500/mm3;
• Platelet count ≥ 100\*109/l;
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
• ALT and AST ≤ 2.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance \> 50 ml/min;
• Prothrombin time or INR \< 1.5 x ULN;
• 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

You may not qualify if:

• Lesion \> 3,5 cm size;
• History of epilepsy;
• Extrahepatic metastases rendering local therapy unfeasible;
• History of cardiac disease:
• Congestive heart failure \>NYHA class 2;
• Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
• Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (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;
• Concomitant use of anti-convulsives and anti-arrhythmic drugs other than beta blockers for antiepileptic or antiarrhythmic purpose;
• Allergy to contrast media;
• Any implanted stimulation device;

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (3)

VU University Medical Center

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Academic Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

Location

Related Publications (2)

• Meijerink MR, Ruarus AH, Vroomen LGPH, Puijk RS, Geboers B, Nieuwenhuizen S, van den Bemd BAT, Nielsen K, de Vries JJJ, van Lienden KP, Lissenberg-Witte BI, van den Tol MP, Scheffer HJ. Irreversible Electroporation to Treat Unresectable Colorectal Liver Metastases (COLDFIRE-2): A Phase II, Two-Center, Single-Arm Clinical Trial. Radiology. 2021 May;299(2):470-480. doi: 10.1148/radiol.2021203089. Epub 2021 Mar 16.

  PMID: 33724066 DERIVED

• Scheffer HJ, Vroomen LG, Nielsen K, van Tilborg AA, Comans EF, van Kuijk C, van der Meijs BB, van den Bergh J, van den Tol PM, Meijerink MR. Colorectal liver metastatic disease: efficacy of irreversible electroporation--a single-arm phase II clinical trial (COLDFIRE-2 trial). BMC Cancer. 2015 Oct 24;15:772. doi: 10.1186/s12885-015-1736-5.

  PMID: 26497813 DERIVED

MeSH Terms

Interventions

Electroporation

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Study Officials

• Martijn R Meijerink, MD, PhD

  VU University Medical Center (VUmc)

  PRINCIPAL INVESTIGATOR

• Krijn P van Lienden, MD, PhD

  Academic Medical Center Amsterdam (AMC)

  PRINCIPAL INVESTIGATOR

• Arian R van Erkel, MD, PhD

  Leiden University Medical Center (LUMC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: Single arm prospective trial with predefined endpoint: accept indication if at least 50% of patients are alive without local tumor progression at 12 months following irreversible electroporation (IRE) treatment for centrally located colorectal cancer liver metastases (CRLM)

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 10, 2014
• Study Start: May 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2020
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

NL (3)