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

NCT ID: NCT02082782

Last Updated: 2022-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-31

Study Completion Date

2020-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Colorectal Liver Metastases

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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irreversible electroporation (IRE)

Single arm study: percutaneous or open irreversible electropration of CRLM

Group Type EXPERIMENTAL

Irreversible electroporation (IRE)

Intervention Type PROCEDURE

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

Interventions

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Irreversible electroporation (IRE)

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

Intervention Type PROCEDURE

Other Intervention Names

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NanoKnife

Eligibility Criteria

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Inclusion 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 more than 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:

* 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

Exclusion Criteria

* 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;
* 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

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Amsterdam UMC, location VUmc

OTHER

Sponsor Role lead

Responsible Party

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Dr. M.R. Meijerink

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martijn R Meijerink, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

VU University Medical Center (VUmc)

Krijn P van Lienden, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Academic Medical Center Amsterdam (AMC)

Arian R van Erkel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center (LUMC)

Locations

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VU University Medical Center

Amsterdam, North Holland, Netherlands

Site Status

Academic Medical Center

Amsterdam, North Holland, Netherlands

Site Status

Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status

Countries

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Netherlands

References

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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.

Reference Type DERIVED
PMID: 33724066 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26497813 (View on PubMed)

Other Identifiers

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COLDFIRE-2 study

Identifier Type: -

Identifier Source: org_study_id