Colorectal Liver MetastasesPhase 1IRENCT01799044
Pilot-study: Non-thermal Ablation Using Irreversible Electroporation to Treat Colorectal Liver Metastases
A Phase 1 study testing Irreversible electroporation (IRE) in people with Colorectal Liver Metastases and Metastatic Liver Disease, run by Dr. M.R. Meijerink at 1 site in Netherlands.
Trial summary
Irreversible electroporation is a new, minimal-invasive image-guided treatment to treat tumors near or around vulnerable structures, such as central liver tumors. To investigate the safety and efficacy of IRE in the treatment of colorectal liver metastases, patients with resectable colorectal liver metastases undergo… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Liver Metastases, Metastatic Liver Disease
- What is being tested?
- Irreversible electroporation (IRE)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2012to Sep 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological or cytological documentation of primary colorectal tumor
- Liver metastases visible on FDG PET-CT or ceCT, size ≤ 3,5 cm and eligible for resection
- Resectability re-confirmed per-operatively by US
- Age > 18 years
- WHO performance status 0 - 2
- Life expectancy of at least 12 weeks
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- 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 ³ 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.
Who cannot join
- Lesion > 3,5 cm size
- History of epilepsy
- 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).
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- 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)
- Uncontrolled infections (> grade 2 NCI-CTC version 3.0).
- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment.
- Immunotherapy ≤ 6 weeks prior to the procedure
- Chemotherapy ≤ 12 weeks prior to the procedure
- Radiotherapy, RFA or MWA treatment of target lesions prior to resection
- Concomitant use of anti-convulsive and anti-arrhythmic drugs other than beta blockers.
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
VU University Medical Center
Amsterdam, North Holland, 1081HV
About this study
Official title: Pilot-study: Non-thermal Ablation Using Irreversible Electroporation (IRE) to Treat Colorectal Liver Metastases - "Ablate and Resect"
Irreversible electroporation is a new, minimal-invasive image-guided treatment to treat tumors near or around vulnerable structures, such as central liver tumors.
To investigate the safety and efficacy of IRE in the treatment of colorectal liver metastases, patients with resectable colorectal liver metastases undergo IRE and resection of the metastases in the same session. After resection, the specimen is examined macroscopically to determine vitality using a specific vitality staining (triphenyl-tetrazoliumchloride) and to visualize the exact ablation zone. Subsequently, histopathologic examination is used to determine type of cell death and the microscopic ablation zone.
The investigators hypothesize that IRE is a safe effective method to treat colorectal liver metastasis and that cell damage and cell death is demonstrated as soon as 1 hour after the procedure.
Read the detailed description
This pilot-study is designed to determine the safety of IRE using the NanoKnife on colorectal liver metastases. Secondary, feasibility, histological effect on the ablated cells and exact shape and size of the ablated area will be determined.
Study design:
Patients with resectable CRLM (1 lesion or more) undergoing surgical resection of the metastases will receive study information to participate in this pilot-study. Limited extrahepatic disease is not contra-indicated.
Patients will undergo a general pre-procedural work-up: total body FDG PET-CT, ceCT of the abdomen, anesthetic review with special attention to cardiac history, baseline full blood examination, urea and electrolytes, renal function tests, liver enzymes and coagulation profile test.
The procedure is conducted under general anaesthesia with muscle relaxants to prevent patient motion and epidural analgesia. A laparotomy will be performed at the surgeon's discretion for optimal liver exposure. Intraoperative ultrasonography (IOUS) will be carried out by an experienced interventional radiologist for exact evaluation of maximum diameter, number and location of all lesions and to confirm resectability (if lesions prove not to be resectable, only RFA will be performed according to standard of care). All lesions will be biopsied. The electrodes will be placed under ultrasound guidance according to manufacturer's guidelines in the lesions that are eligible for resection. After correct placement of the electrodes the lesions will be ablated according to protocol with ECG synchronization and the ablation zone is determined by US.
During the procedure the cardiac rhythm will be closely monitored and a defibrillator will be present at all times.
After IOUS confirmation of complete ablation (at least 30 minutes after ablation of the lesion) the surgeon will perform a partial liver resection / metastasectomy including the ablated lesions and the surgical procedure is ended as usual. After the treatment of all lesions with the NanoKnife and before resection (and RFA of unresectable CRLM if indicated), blood samples will be drawn to determine renal function and liver enzymes since cell destruction may cause biochemical abnormalities.
The resected specimen will be transported to the department of pathology. After sectioning, the specimen will be photographed extensively to determine exact shape and size of the ablated area. One slice is stained in vitality-staining (TTC), to macroscopically distinguish viable from nonviable tissue.
After formalin fixation, the specimen is stained and examined under light microscopy according to standard protocol to determine radicality of the resection margins. Additionally, special attention will be given to indications for cellular damage, vessel wall damage and size and shape of the ablation zone. Caspase-3 and BAX/BCL-2 analysis will be performed to investigate the induction of apoptosis. The results will be compared to the result of the biopsy taken prior to ablation.
On day one and day three post-operatively regular blood samples will be drawn, including liver enzymes and renal function tests. After discharge, out of hospital follow-up will be according to liver surgery protocol. The investigators aim to include 10 patients in this pilot study.
Monitoring:
An independent monitor (quality officer) will monitor all study data according to Good Clinical Practice (GCP). The informed consent of selected individual participants will be checked. Source Data verification will be performed during onsite monitoring (to verify if all data on the Case Report Form are in accordance with the source data). The intensity of this verification is in relation to the risk associated with the intervention investigated. Data that by all means will be checked are the informed consent form, in- and exclusion criteria and the primary outcome. The monitor will also verify if all (S)AE's and SUSAR's are reported adequately and within the time that is determined by legal rules and regulations.
- Being tested
- Irreversible electroporation (IRE)
- Keywords
- Irreversible electroporation, IRE, Electroporation, Colorectal liver metastases, CRLM, Safety, Feasibility, Efficacy, Single-center, Low Energy Direct Current, Ablate-and-resect, Nonthermal ablation, Ablation
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irreversible electroporation (IRE)Device
Also called IRE, NanoKnife
Tumor ablation with irreversible electroporation with the NanoKnife
| Study group | Role | What they receive |
|---|---|---|
| Irreversible electroporation | Experimental | Single arm study: Irreversible electroporation of colorectal liver metastasis Receives: Device: Irreversible electroporation (IRE) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Safety using Common terminology Criteria for Adverse Events (CTCAE). Since the ablated tissue will be resected we expect procedure-related complications to occur mainly during the procedure.
Measured: participants will be followed for the duration of hospital stay, an expected average of 1 week
Secondary outcomes (1)
Efficacy
Cell death of CRLM after IRE is demonstrated macroscopically by using vitality-staining with triphenyl-tetrazoliumchloride (TTC). Since and shape of the ablation zone is assessed. Immunohistologic examination is used to more specifically assess microscopic cell damage and vessel wall damage. Apoptotic markers are used.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study startNov 2012
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Liver MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective ablate and resect trial where 10 patients with resecatble colorectal liver metastases were treated with irrevrsible electroporation approximately 2 hours before the tumors were resected.
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. M.R. Meijerink
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam UMC, location VUmc
- Responsible party
- Sponsor-investigator, Dr. M.R. Meijerink, Amsterdam UMC, location VUmc
- Investigators
- Martijn R Meijerink, MD, PhD, Principal investigator, Amsterdam UMC, location VUmcPetrousjka M van den Tol, MD, PhD, Principal investigator, Amsterdam UMC, location VUmcC van Kuijk, Prof. Dr., Study director, VU University Medical Center, head of department of radiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01799044
- Sponsor's protocol ID
- NL 41089.029.12 COLDFIRE
- Acronym
- IRE
- Status last verified
- Dec 2022
- First submitted
- 20 Feb 2013
- Last updated
- 20 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot-study: Non-thermal Ablation Using Irreversible Electroporation (IRE) to Treat Colorectal Liver Metastases - "Ablate and Resect"
- ClinicalTrials.gov ID
- NCT01799044
- Acronym / sponsor ID
- IRE / NL 41089.029.12 COLDFIRE
- Keywords
- Irreversible electroporation, IRE, Electroporation, Colorectal liver metastases, CRLM, Safety, Feasibility, Efficacy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Dr. M.R. MeijerinkUniversity, hospital or other
- Collaborators
- Amsterdam UMC, location VUmc
- Study start
- Nov 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 26 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Irreversible electroporation is a new, minimal-invasive image-guided treatment to treat tumors near or around vulnerable structures, such as central liver tumors.
To investigate the safety and efficacy of IRE in the treatment of colorectal liver metastases, patients with resectable colorectal liver metastases undergo IRE and resection of the metastases in the same session. After resection, the specimen is examined macroscopically to determine vitality using a specific vitality staining (triphenyl-tetrazoliumchloride) and to visualize the exact ablation zone. Subsequently, histopathologic examination is used to determine type of cell death and the microscopic ablation zone.
The investigators hypothesize that IRE is a safe effective method to treat colorectal liver metastasis and that cell damage and cell death is demonstrated as soon as 1 hour after the procedure.
Detailed description
This pilot-study is designed to determine the safety of IRE using the NanoKnife on colorectal liver metastases. Secondary, feasibility, histological effect on the ablated cells and exact shape and size of the ablated area will be determined.
Study design:
Patients with resectable CRLM (1 lesion or more) undergoing surgical resection of the metastases will receive study information to participate in this pilot-study. Limited extrahepatic disease is not contra-indicated.
Patients will undergo a general pre-procedural work-up: total body FDG PET-CT, ceCT of the abdomen, anesthetic review with special attention to cardiac history, baseline full blood examination, urea and electrolytes, renal function tests, liver enzymes and coagulation profile test.
The procedure is conducted under general anaesthesia with muscle relaxants to prevent patient motion and epidural analgesia. A laparotomy will be performed at the surgeon's discretion for optimal liver exposure. Intraoperative ultrasonography (IOUS) will be carried out by an experienced interventional radiologist for exact evaluation of maximum diameter, number and location of all lesions and to confirm resectability (if lesions prove not to be resectable, only RFA will be performed according to standard of care). All lesions will be biopsied. The electrodes will be placed under ultrasound guidance according to manufacturer's guidelines in the lesions that are eligible for resection. After correct placement of the electrodes the lesions will be ablated according to protocol with ECG synchronization and the ablation zone is determined by US.
During the procedure the cardiac rhythm will be closely monitored and a defibrillator will be present at all times.
After IOUS confirmation of complete ablation (at least 30 minutes after ablation of the lesion) the surgeon will perform a partial liver resection / metastasectomy including the ablated lesions and the surgical procedure is ended as usual. After the treatment of all lesions with the NanoKnife and before resection (and RFA of unresectable CRLM if indicated), blood samples will be drawn to determine renal function and liver enzymes since cell destruction may cause biochemical abnormalities.
The resected specimen will be transported to the department of pathology. After sectioning, the specimen will be photographed extensively to determine exact shape and size of the ablated area. One slice is stained in vitality-staining (TTC), to macroscopically distinguish viable from nonviable tissue.
After formalin fixation, the specimen is stained and examined under light microscopy according to standard protocol to determine radicality of the resection margins. Additionally, special attention will be given to indications for cellular damage, vessel wall damage and size and shape of the ablation zone. Caspase-3 and BAX/BCL-2 analysis will be performed to investigate the induction of apoptosis. The results will be compared to the result of the biopsy taken prior to ablation.
On day one and day three post-operatively regular blood samples will be drawn, including liver enzymes and renal function tests. After discharge, out of hospital follow-up will be according to liver surgery protocol. The investigators aim to include 10 patients in this pilot study.
Monitoring:
An independent monitor (quality officer) will monitor all study data according to Good Clinical Practice (GCP). The informed consent of selected individual participants will be checked. Source Data verification will be performed during onsite monitoring (to verify if all data on the Case Report Form are in accordance with the source data). The intensity of this verification is in relation to the risk associated with the intervention investigated. Data that by all means will be checked are the informed consent form, in- and exclusion criteria and the primary outcome. The monitor will also verify if all (S)AE's and SUSAR's are reported adequately and within the time that is determined by legal rules and regulations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective ablate and resect trial where 10 patients with resecatble colorectal liver metastases were treated with irrevrsible electroporation approximately 2 hours before the tumors were resected.
| Arm | Type | Receives |
|---|---|---|
| Irreversible electroporation | Experimental | Device: Irreversible electroporation (IRE)Single arm study: Irreversible electroporation of colorectal liver metastasis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histological or cytological documentation of primary colorectal tumor
- Liver metastases visible on FDG PET-CT or ceCT, size ≤ 3,5 cm and eligible for resection
- Resectability re-confirmed per-operatively by US
- Age > 18 years
- WHO performance status 0 - 2
Key exclusion criteria (17 listed)
- Lesion > 3,5 cm size
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Irreversible electroporation (IRE)Also: IRE, NanoKnifeTumor ablation with irreversible electroporation with the NanoKnife | Device | Irreversible electroporation |
Primary outcome
Safety
Time frame: participants will be followed for the duration of hospital stay, an expected average of 1 week
Safety using Common terminology Criteria for Adverse Events (CTCAE). Since the ablated tissue will be resected we expect procedure-related complications to occur mainly during the procedure.
1 secondary outcome
Efficacy
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martijn R Meijerink, MD, PhD principal investigator
Amsterdam UMC, location VUmc
Petrousjka M van den Tol, MD, PhD principal investigator
Amsterdam UMC, location VUmc
C van Kuijk, Prof. Dr. study director
VU University Medical Center, head of department of radiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Irreversible electroporation (IRE) in people with Colorectal Liver Metastases and Metastatic Liver Disease, run by Dr. M.R. Meijerink at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: participants will be followed for the duration of hospital stay, an expected average of 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2022; AzTrials last refreshed its copy on 1 Nov 2026.